1,972 research outputs found
Sorveglianza molecolare della resistenza ai derivati dell’artemisinina e ad altri antimalarici in isolati di Plasmodium falciparum africani
No full textL’introduzione della terapia combinata a base di artemisinina (artemisinin-based combination therapy, ACT) ha rappresentato una svolta epocale nella lotta contro la malaria da Plasmodium falciparum, riducendo drasticamente la morbilità e mortalità da questa causate. Purtroppo, la diffusione della resistenza di P. falciparum all'artemisinina nel Sud-Est Asiatico costituisce una reale minaccia per il controllo e l’eliminazione della malaria, poiché rischia di vanificare i successi raggiunti nell’ultimo decennio, soprattutto in termini di sopravvivenza infantile. Numerosi studi, condotti su isolati di P. falciparum provenienti dal Sud-Est Asiatico, hanno dimostrato che la resistenza all’artemisinina è strettamente legata alla presenza di polimorfismi a singolo nucleotide (SNPs) nel gene kelch 13 (k13). Alcuni di questi SNPs sono anche stati descritti in Africa, ma mai nessuno è stato correlato ad un’aumentata tolleranza o resistenza all'artemisinina (Ménard et al., 2016). La recente introduzione di strumenti di biologia molecolare di nuova generazione, volti alla rapida e precoce individuazione di parassiti resistenti, consente di perfezionare e rendere più accurate le strategie terapeutiche e profilattiche impiegate nei casi di malaria da P. falciparum. In questo lavoro di tesi, al fine di identificare la presenza di mutazioni puntiformi nel gene k13 di P. falciparum, sono stati analizzati, mediante PCR e sequenziamento diretto, 930 isolati di P. falciparum raccolti in quattro paesi africani nei quali la malaria continua a rappresentare un importante problema di salute pubblica: Camerun, Eritrea, Botswana, e Guinea Conakry. Per i campioni provenienti dal Camerun e dall’Eritrea, lo screening molecolare è stato effettuato tramite il sequenziamento di nuova generazione NGS, ovvero un sistema standardizzato di sorveglianza della farmaco-resistenza ad alto rendimento. Oltre all’analisi del gene Pfk13, è stata valutata l’eventuale presenza di mutazioni nei diversi geni marcatori di resistenza per gli antimalarici comunemente impiegati nelle combinazioni terapeutiche a base di artemisinina. Inoltre, in collaborazione con il CDC (Centre for Disease Control and Prevention) di Atlanta, è stato messo a punto un nuovo metodo di rilevazione dell’espressione del gene plasmepsina 2 di P. falciparum, coinvolto nella resistenza alla piperachina. I risultati dello studio di sorveglianza molecolare qui riportati non hanno evidenziato alcuna resistenza all'artemisinina. Tuttavia, per gli altri marcatori molecolari indagati, è stata identificata un’alta frequenza di varianti alleliche associate alla resistenza alle diverse classi di farmaci antimalarici. Questi risultati suggeriscono la forte necessità di effettuare una costante valutazione di efficacia terapeutica dei farmaci impiegati nel trattamento della malaria da P. falciparum, e un assiduo monitoraggio molecolare della farmaco-resistenza, al fine di sviluppare adeguate strategie di controllo e prevenzione della malaria
A paradigmatic autistic phenotype associated with loss of PCDH11Y and NLGN4Y genes
No full textBackground: Most studies relative to Y chromosome abnormalities are focused on the sexual developmental disorders. Recently, a few studies suggest that some genes located on Y chromosome may be related to different neurodevelopment disorders. Case presentation: We report a child with sexual developmental disorder associated with a peculiar phenotype characterized by severe language impairment and autistic behaviour associated with a mosaicism [45,X(11)/46,XY(89)] and a partial deletion of the short and long arm of Y chromosome (del Yp11.31q11.23) that also involves the loss of both PCDH11Y and NLGN4Y genes. To our knowledge no study has ever reported the occurrence of the lack of both PCDH11Y and NLGN4Y located in the Y chromosome in the same patient. Conclusions: We hypothesized a functional complementary role of PCDH11Y and NLGN4Y within formation/maturation of the cerebral cortex. The impairment of early language development may be mainly related to the lack of PCDH11Y that underlies the early language network development and the later appearance of the autistic behaviour may be mainly related to deficit of inhibitory glicinergic neurotransmission NLGN4Y-linked
The osteoblastic differentiation of dental pulp stem cells and bone formation on different titanium surface textures.
No full textBone Tissue Engineering (BTE) and Dental Implantology (DI) require the integration of implanted structures, with well characterized surfaces, in bone. In this work we have challenged acid-etched titanium (AET) and Laser Sintered Titanium (LST) surfaces with either human osteoblasts or stem cells from human dental pulps (DPSCs), to understand their osteointegration and clinical use capability of derived implants. DPSCs and human osteoblasts were challenged with the two titanium surfaces, either in plane cultures or in a roller apparatus within a culture chamber, for hours up to a month. During the cultures cells on the titanium surfaces were examined for histology, protein secretion and gene expression. Results show that a complete osteointegration using human DPSCs has been obtained: these cells were capable to quickly differentiate into osteoblasts and endotheliocytes and, then, able to produce bone tissue along the implant surfaces. Osteoblast differentiation of DPSCs and bone morphogenetic protein production was obtained in a better and quicker way, when challenging stem cells with the LST surfaces. This successful BTE in a comparatively short time gives interesting data suggesting that LST is a promising alternative for clinical use in DI
Recurrent missense variant in the nuclear export signal of FMR1 associated with FXS-like phenotype including intellectual disability, ASD, facial abnormalities
No full textFragile X syndrome (FXS; MIM 300624) is an X-linked genetic disorder characterized by physical abnormalities associated with intellectual disability and a wide spectrum of neurological and psychiatric impairments. FXS occurs more frequently in males, 1 in 5000 males and 1 in 8000 females accounting for 1–2% of overall intellectual disability (ID). In more than 99% of patients, FXS results from expansions of a CGG triplet repeat (>200 in male) of the FMR1 gene. In the last years an increasing number, albeit still limited, of FXS subjects carrying FMR1 mutations including deletions, splicing errors, missense, and nonsense variants was reported. Nevertheless, the studies concerning the functional consequences of mutations in the FMR1 gene are rare so far and, therefore, we do not have sufficient knowledge regarding the genotype/phenotype correlation. We report a child carrying a hemizygous missense FMR1 (NM_002024.5:c.1325G > A p.Arg442Gln) variant, maternally inherited, associated with facial abnormalities, developmental delay, and social and communication deficits assessed with formal neuropsychological tests. The study contributes to highlighting the clinical differences between the CGG triplet repeat dependent phenotype and FMR1variant dependent phenotype and it also confirms the pathogenicity of the variant being reported for the second time in the literature
Electroclinical features and outcome of ANKRD11-related KBG syndrome: A novel report and literature review
No full textKBG syndrome (OMIM #148050) is a rare autosomal dominant
disorder, typically characterized by macrodontia of the upper central
incisors, distinct craniofacial findings, short stature, and skeletal
anomalies associated with neurological involvement including intellectual disability, behaviour difficulties, and epilepsy. KBG syndrome is
associated with mutations in ANKRD11 gene that plays a chromatin
regulator role of histone acetylation and gene expression during neurogenesis in the embryonic brain
Commonalities and distinctions between two neurodevelopmental disorder subtypes associated with SCN2A and SCN8A variants and literature review
No full textThis study was aimed to analyze the commonalities and distinctions of voltage-gated sodium channels, Nav1.2, Nav1.6, in neurodevelopmental disorders. An observational study was performed including two patients with neurodevelopmental disorders. The demographic, electroclinical, genetic, and neuropsychological characteristics were analyzed and compared with each other and then with the subjects carrying the same genetic variants reported in the literature. The clinical features of one of them argued for autism spectrum disorder and developmental delay, the other for intellectual disability, diagnoses confirmed by the neuropsychological assessment. The first patient was a carrier of SCN2A (p.R379H) variant while the second was carrier of SCN8A (p.E936K) variant, both involving the pore loop of the two channels. The results of this study suggest that the neurodevelopmental disorders without overt epilepsy of both patients can be the consequences of loss of function of Nav1.2/Nav1.6 channels. Notably, the SCN2A variant, with an earlier expression timing in brain development, resulted in a more severe phenotype as autism spectrum disorder and developmental delay, while the SCN8A variant, with a later expression timing, resulted in a less severe phenotype as intellectual disability
The extended hard X-ray emission from the Vela Plerion
No full textWe present the results of a broad band (3-200 keV) spectral analysis of BeppoSAX and XMM-Newton observations of the Vela plerion. The hard X-ray (> 15 keV) emission is found to be extended over a region of 12'-15' radius, corresponding to a size of about 1.0-1.3 pc for a source distance of 290 pc. A single power law does not give an acceptable fit while a broken power law or a log-parabolic law nicely fit the data. The former spectral model has the photon index Gamma(1) = 1.66 +/- 0.01 for energies lower than the break value equal to 12.5 keV and the index Gamma(2) = 2.01 +/- 0.05 up to about 200 keV. The total X-ray luminosity of the Vela plerion is L-X = 5.5 x 10(33) erg s(-1), which implies a conversion factor of the spin-down power of similar to 10(-3)
Geni di virulenza in ceppi di Escherichia coli isolati da conigli con sintomatologia enterica in allevamenti intensivi dell’Italia Meridionale
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