Nucleosome occupancy reveals regulatory elements of the CFTR promoter

Access to regulatory elements of the genome can be inhibited by nucleosome core particles arranged along the DNA strand. Hence, sites that are accessible by transcription factors may be located by using nuclease digestion to identify the relative nucleosome occupancy of a genomic region. In order to define novel cis regulatory elements in the ∼2.7-kb promoter region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, we define its nucleosome occupancy. This profile reveals the precise positions of nucleosome-free regions (NFRs), both cell-type specific and others apparently unrelated to CFTR-expression level and offer the first high-resolution map of the chromatin structure of the entire CFTR promoter in relevant cell types. Several of these NFRs are strongly bound by nuclear factors in a sequence-specific manner, and directly influence CFTR promoter activity. Sequences within the NFR1 and NFR4 elements are highly conserved in many human gene promoters. Moreover, NFR1 contributes to promoter activity of another gene, angiopoietin-like 3 (ANGPTL3), while NFR4 is constitutively nucleosome-free in promoters genome wide. Conserved motifs within NFRs of the CFTR promoter also show a high level of protection from DNase I digestion genome-wide, and likely have important roles in the positioning of nucleosome core particles more generally

Different immunohistochemical levels of Hsp60 and Hsp70 in a subset of brain tumors and putative role of Hsp60 in neuroepithelial tumorigenesis

<p>In this work we analysed, by immunohistochemistry, a series of brain tumors to detect the levels and cellular distribution of Hsp60 and Hsp70. We found that Hsp60 levels were significantly higher than those of Hsp70 in neuroepithelial tumors, while levels of both molecules were not significantly different from each other in meningeal neoplasms. In particular, Hsp60 immunopositivity was present mainly at the cytoplasmic level, while Hsp70 immunopositivity was found both in the cytoplasm and in the nucleus of tumor cells. The levels of these molecules in healthy control cells were always very low. Finally, Hsp60 and Hsp70 levels did not correlate with the different types (WHO grade) of neoplasm. Our results are partially in agreement with previous studies and suggest that Hsp60 is not increased by a passive phenomenon (<em>e.g</em>., due to the stress caused by the peritumor environment on cancer cells) but may be actively implicated in tumor progression, <em>e.g</em>. inhibiting tumor cell death or antitumor immune system response, as already postulated <em>in vitro</em>. We also briefly discuss the most recent publications on the extramitochondrial localization of Hsp60 in tumor cells and its role in tumor progression.</p><br /

Botulinum toxin for the treatment of dystonia and pain in corticobasal syndrome

Background: Dystonia is a key symptom in corticobasal syndrome (CBS), and upper limb dystonia is the most common phenotype. Dystonia-associated pain is frequently reported and can be disabling, with poor benefit from oral treatments. Aims of the Study: To investigate the role of botulinum toxin A (BoTNA) in the treatment of dystonia and associated pain in CBS. Methods: Ten consecutive patients with a clinical diagnosis of probable CBS and dystonia with/without associated pain were treated with BoTNA every 3&nbsp;months. Treatment efficacy was assessed during the first follow-up visit, three months after the first injection, by means of caregiver impression (CI), evaluation of muscle tone with the Ashworth scale (AS), severity of pain measured with the visual analog scale (VAS). Results: Nine subjects underwent at least three treatments, four patients discontinued for progressive reduction in efficacy or disease progression, five patients are ongoing with good response, and one completed the 10th treatment. No local or systemic side effects were reported, and levodopa equivalent daily dose remained unchanged in most cases during the observational period. Significant improvement of AS was recorded (from 2.9&nbsp;±&nbsp;0.7 to 2.0&nbsp;±&nbsp;0.5, p = 0.003). CI ranged from mild to moderate benefit. All patients reported efficacy on pain, with a significant reduction of VAS score (from 7.7&nbsp;±&nbsp;1.7 to 1.7&nbsp;±&nbsp;0.7 in the Pain group, p = 0.016). Conclusions: Our study confirms safety, efficacy, and tolerability of BoTNA in the treatment of dystonia associated with CBS. Local treatment should be considered as a valid alternative to oral treatment modulation mainly in the presence of associated pain

Theory of mind in Parkinson’s disease: evidences in drug-naïve patients and longitudinal effects of dopaminergic therapy

Theory of mind (ToM) is the ability to attribute mental states to one self and others and to understand that others have beliefs different from one’s own. Different subcomponents of ToM have also been identified: cognitive and affective. Cognitive ToM refers to the capacity to infer others’ beliefs and intentions, while affective ToM implies the ability to appreciate others’ emotional states. The aim of this study was to explore ToM in drug-naïve Parkinson’s disease (PD) patients and to investigate the effects of chronic dopaminergic therapy on different subcomponents of ToM during a 3&nbsp;months and 1&nbsp;year of follow-up. We examined 16 PD patients in three conditions: before (un-medicated) and after dopaminergic therapy (medicated 3&nbsp;months: T1 and medicated 1&nbsp;year: T2). We also compared our PD’s ToM abilities with 11 healthy individuals. ToM was explored with 5 different tasks: Faux Pas Test, Picture Sequencing Task Capture Story, Emotion Attribution Task, Strange Stories Task, and Karolinska Directed Emotional Faces. Our study confirms that PD patients present deficits in cognitive components of ToM and preserved performances in the affective ones in early stages of disease. We also find a significant effect of dopaminergic therapy on ToM already after 3&nbsp;months with a good persistency after 1&nbsp;year of treatment

Active faults and inferred seismic sources in the San Vito lo Capo peninsula, northwestern Sicily, Italy

Two independent active faults, capable of generating medium-sized earthquakes in the San Vito lo Capo peninsula, northwestern Sicily (Italy) have been identified as a result of detailed field studies. In western Sicily, instrumental seismicity is low; in fact, except for the 1968 Belice earthquake (Ms = 5.4), historical records indicate that this area is relatively quiescent. Most of the seismicity is in the offshore sector of the Sicilian Maghrebian Chain, which is characterized by several medium- to low-magnitude events. The main shock of the 2002 Palermo seismic sequence (Mw = 5.9) represents the largest earthquake felt in the area in recent years. The deformation pattern characterizing the most recent faults mapped in northwestern Sicily includes a grid of high-angle faults consisting of major east-west-striking right-lateral and north-south-striking left-lateral features. This fault grid is related to a regional transcurrent right-lateral shear zone, here named the UEKA shear zone, bounded to the north by the Ustica-Eolie fault and to the south by the Kumeta-Alcantara fault. The UEKA shear zone accommodates the regional strain induced by the current stress field acting in the area, which, as emerges from both structural and seismological data, is characterized by a NW-SE-striking main compression