1,720,964 research outputs found
Advances in understanding - genetic basis of intellectual disability
Full text linkIntellectual disability is the most common developmental disorder characterized by a congenital limitation in intellectual functioning and adaptive behavior. It often co-occurs with other mental conditions like attention deficit/hyperactivity disorder and autism spectrum disorder, and can be part of a malformation syndrome that affects other organs. Considering the heterogeneity of its causes (environmental and genetic), its frequency worldwide varies greatly. This review focuses on known genes underlying (syndromic and non-syndromic) intellectual disability, it provides a succinct analysis of their Gene Ontology, and it suggests the use of transcriptional profiling for the prioritization of candidate genes
The FRAXopathies: Definition, overview, and update
No full textThe fragile X syndrome, fragile X tremor ataxia syndrome, and premature ovarian insufficiency are conditions related tot he X chromosome folate-sensitive site FRAXA. Threfore, we propose that they are considered as a family of disorders under the general designation of FRAXopathies. The present reviwe will outline the main clinical and molecular features of these disorders, with special emphasis on the pathogenic mechanisms that lead to distinct phenotypes, starting from related mutations. The understanding of these mechanisms is already generating promising therapeutic approache
Bioconversion of lignocellulosic biomass to bioethanol and biobutanol
No full textLignocellulosic biomass that is obtained as agriculture by-products and/or industrial residues is a nonfoodstuff competitive feedstock for the sustainable production of important liquid fuels such as bioethanol or biobutanol and chemical products through the biorefinery processes. Cellulose, hemicellulose, and lignin are the main components of lignocellulosic biomass. From the biochemical point of view, high amounts of sugars present in cellulose and hemicellulose can be chemically produced, using acid as the catalyst, or enzymatically hydrolyzed and converted into biofuels by a fermentation process. Pretreatment technologies based on biological approaches are interesting to improve the efficiency of the bioconversion processes and to overcome barriers in the scale-up and commercialization of renewable biorefineries. In this chapter, after a brief introduction, a preliminary analysis of suitable strains and their productivity is done in the first part, with reference to processes involved both in bioethanol and biobutanol production. During the bioethanol production from lignocellulosic biomass, pretreated lignocelluloses are converted to simple sugars, in hydrolysis reactors, by catabolic enzymes, and consequently, enzymatic hydrolysis of lignocellulosic biomass is then described, under different points of view. Operating conditions, methodologies, and biochemical aspects of enzymatic hydrolysis are described with economic and energetic considerations in the second part. Apart from that, traditional downstream purification and membrane-assisted enzymatic hydrolysis as innovative methods are compared too in this chapter. The hydrolyzate is fermented to ethanol by ethanologenic yeasts, separate enzymatic hydrolysis and fermentation (SHF), which is still the main process configuration for the biofuels production from lignocellulose. In order to overcome the SHF limitations, integrated conversion technologies have been developed, including simultaneous saccharification and fermentation, simultaneous saccharification and cofermentation, and consolidated bioprocessing. All these processes are described in the third part of the chapter. Several different pretreatment methods (physical, chemical, biological, electrical, or a combination of these) promote the lignocellulose breakdown, reducing recalcitrance biomass and facilitating enzymes to access their substrates. However, pretreatment processes of lignocellulosic materials cause the formation of numerous lignocellulose-derived by-products that can inhibit microbial growth and fermentation yields. A detailed description of the effect of fermentation inhibitors such as furan derivatives, weak acid (acetic, formic, and levulinic acids), phenols, and other inhibitors is done in the concluding part of the chapter. Some strategies are also suggested for minimizing inhibitor effects
Bradeion (SEPT4) as a Urinary Marker of Transitional Cell Bladder Cancer: A Real-Time Polymerase Chain Reaction Study of Gene Expression
No full textWe evaluated whether Bradeion/SEPT4 gene expression could be used as a potential urinary marker to diagnose bladder transitional cell carcinoma. From 2005 to 2007 we collected urine samples from 58 individuals, 17 healthy controls and 41 patients in whom bladder tumors were previously diagnosed by cystoscopy. Urine was collected from all patients before transurethral resection of bladder tumor. We performed real-time reverse transcriptase-polymerase chain reaction to evaluate Bradeion/SEPT4 transcript levels using urine sample mRNA. Statistical analysis was done with the Mann-Whitney test and ROC curves. Pathological examination of bladder tumor specimens revealed transitional cell bladder cancer. According to the 2002 TNM classification stage was Ta in 11 patients, T1 in 18 and T2/T3 in 12. All patients had G2 or G3 tumors according to the 1973 WHO grade classification. Relative quantification analysis of Bradeion transcript showed significantly increased levels compared to controls, namely 21.85 times higher in Ta stage tumors, 7.21 times higher in T1 tumors and 4.36 times higher in grade T2/T3 tumors. We compared each tumor stage group with the control group using the Mann-Whitney test to verify the statistical significance of observed differences. The ROC curve built on the change in threshold cycle revealed that with this method we attained 92.68% sensitivity and 64.71% specificity (AUC 0.798, p = 0.0001). Bradeion/SEPT4 transcript levels are significantly increased in patients with transitional cell bladder cancer compared to healthy controls. Our preliminary study supports the possible usefulness of Bradeion as a urinary marker of urothelial disease
The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the mutant FMR1 gene in vitro.
No full textFragile X syndrome (FXS), the leading cause of inherited mental retardation, is due to expansion and methylation of a CGG sequence in the FMR1 gene, which result in its silencing and consequent absence of FMRP protein. This absence causes loss of repression of metabotropic glutamate receptor 5 (mGluR5)-mediated pathways resulting in the behavioral and cognitive impairments associated with FXS. In a randomized, double-blind trial it was recently demonstrated a beneficial effect of AFQ056, a selective inhibitor of metabotrobic glutamate receptor type 5 (mGluR5), on fully methylated FXS patients respect to partially methylated FXS ones.
METHODS: To determine whether AFQ056 may have secondary effects on the methylation and transcription of FMR1, here we treated three FXS lymphoblastoid cell lines and one normal control male line. A quantitative RT-PCR was performed to assess transcriptional reactivation of the FMR1 gene. To assess the methylation status of the FMR1 gene promoter it was carried out a bisulphite sequencing analysis.
RESULTS: Both FMR1-mRNA levels and DNA methylation were unmodified with respect to untreated controls.
CONCLUSIONS: These results demonstrate that the AFQ056 effect on fully methylated FXS patients is not due to a secondary effect on DNA methylation and consequent transcriptional activation of FMR1
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Insertion of 16 amino acids in the BAR domain of the oligophrenin 1 protein causes mental retardation and cerebellar hypoplasia in an Italian family
No full textWe observed a three-generation family with two maternal cousins and an uncle affected by mental retardation (MR) with cerebellar hypoplasia. X-linked inheritance and the presence of cerebellar malformation suggested a mutation in the OPHN1 gene. In fact, mutational screening revealed a 2-bp deletion that abolishes a donor splicing site, resulting in the inclusion of the initial 48 nucleotides of intron 7 in the mRNA. This mutation determines the production of a mutant oligophrenin 1 protein with 16 extra amino acids inserted in-frame in the N-terminal BAR (Bin1/amphiphysin/Rvs167) domain. This is the first case of a mutation in OPHN1 that does not result in the production of a truncated protein or in its complete loss. OPHN1 (ARHGAP41) encodes a GTPase-activating (GAP) protein belonging to the GRAF subfamily characterized by an N-terminal BAR domain, followed by a pleckstrin-homology (PH) domain and the GAP domain. GRAF proteins play a role in endocytosis and are supposed to dimerize via their BAR domain, that induces membrane curvature. The extra 16 amino acids cause the insertion of 4.4 turns in the third alpha-helix of the BAR domain and apparently impair the protein function. In fact, the clinical phenotype of these patients is identical to that of patients with loss-of-function mutations
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