BCI-assisted training for upper limb motor rehabilitation: estimation of effects on individual brain connectivity and motor functions

The aim of the study is to quantify individual changes in scalp connectivity patterns associated to the affected hand movement in stroke patients after a 1-month training based on BCIsupported motor imagery to improve upper limb motor recovery. To perform the statistical evaluation between pre- and post-training conditions at the single subject level, a resampling approach was applied to EEG datasets acquired from 12 stroke patients during the execution of a motor task with the stroke affected hand before and after the rehabilitative intervention. Significant patterns of the network reinforced after the training were extracted and a significant correlation was found between indices related to the reinforced pattern and the clinical outcome indicated by clinical scales

Modulation of different clusterin isoforms in human colon tumorigenesis

Clusterin is a ubiquitous secretory heterodimeric disulfide-linked glycoprotein, which is implicated in several physiological processes, including immune regulation, cell adhesion and morphological transformation, lipid transportation, tissue remodelling, membrane recycling and cell-cell interactions. A large number of studies have focused their interest on clusterin gene products as mediators of cell cycle progression and cell death induction, although data on the different isoforms and their role in the different cell processes are still obscure. Recently, an increased clusterin expression in breast cancer has been reported. In order to elucidate the role of clusterin in tumor progression and whether one of its isoforms is preferentially expressed in tumorigenesis, we examined its presence throughout the different steps of human colon carcinoma, one of the best-characterized models of human tumor progression. The immunohistochemical observation of 30 bioptic and surgical colon specimens demonstrated a cell compartment clusterin translocation from the nucleus to the cytoplasm directly related to tumor progression. In fact, a nuclear localization found in healthy colonic mucosa is consistent with the involvement of the proapoptotic nuclear form in the regulation of cell cycle progression and in cell death induction. The progression towards high-grade and metastatic carcinoma leads to cytoplasmic clusterin distribution. Protein extracts from freshly isolated cells of the same patients confirm in high-grade carcinomas with metastatic nodes the complete loss of the proapoptotic nuclear form and a cytoplasmic overexpression of the highly glycosylated form. Data obtained from in vitro experiments confirm that this form is released in the extracellular space and corresponded to the fully glycosylated one. These data suggest that the controversial data on clusterin function in tumors may be related to the pattern shift of its isoform production. As the secreted form of clusterin is correlated to cell matrix formation, cell membrane remodeling and cell-cell adhesion, the overexpression of this form in highly aggressive tumors and metastatic nodes could be a potential new prognostic and predictive marker for colon carcinoma aggressiveness

Cocaine-related cervical spinal cord infarction: a case report and review of the literature

Study design Case report. Objectives To report a clinical case of spinal cord infarction due to cocaine use. Setting Spinal Center, IRCCS Fondazione S. Lucia, Rome (Italy). Case presentation Two days after recreational use of cocaine, a 27-year-old Caucasic man was admitted to the emergency department for acute cervical pain, weakness in all four limbs, and urinary retention. A cervical spinal magnetic resonance imaging scan, performed after 2 days, showed a "pencil-like" lesion extending from C4 to T1 metamer, compatible with acute ischemia in the anterior spinal artery territory. Other causes of vascular disorders, as well as inflammatory and infectious disorders were ruled out. At admission in our department, the patient had an incomplete tetraplegia at level C6, an indwelling catheter, and was unable to stand and walk. After 3 months of rehabilitation, he had an AIS score D tetraplegia at level C7, was able to stand and walk using parallel bars, and indwelling catheter was replaced by intermittent catheterization. Discussion and conclusions The etiology of medullary infarction may remain unexplained in nearly 30-40% of cases. Even if rare, cocaine-induced ischemic myelopathy should be considered and ruled out in the differential diagnosis of any acute nontraumatic myelopathy, especially in young patients

Duplex DNA from Sites of Helicase-Polymerase Uncoupling Links Non-B DNA Structure Formation to Replicative Stress

BACKGROUND: Replication impediments can produce helicase-polymerase uncoupling allowing lagging strand synthesis to continue for as much as 6 kb from the site of the impediment. MATERIALS AND METHODS: We developed a cloning procedure designed to recover fragments from lagging strand near the helicase halt site. RESULTS: A total of 62% of clones from a p53-deficient tumor cell line (PC3) and 33% of the clones from a primary cell line (HPS-19I) were within 5 kb of a G-quadruplex forming sequence. Analyses of a RACK7 gene sequence, that was cloned multiple times from the PC3 line, revealed multiple deletions in region about 1 kb from the cloned region that was present in a non-B conformation. Sequences from the region formed G-quadruplex and i-motif structures under physiological conditions. CONCLUSION: Defects in components of non-B structure suppression systems (e.g. p53 helicase targeting) promote replication-linked damage selectively targeted to sequences prone to G-quadruplex and i-motif formation

Distinctive physiological muscle synergy patterns define the Box and Block Task execution as revealed by electromyographic features

Stroke survivors experience muscular pattern alterations of the upper limb that decrease their ability to perform daily-living activities. The Box and Block test (BBT) is widely used to assess the unilateral manual dexterity. Although BBT provides insights into functional performance, it returns limited information about the mechanisms contributing to the impaired movement. This study aims at exploring the BBT by means of muscle synergies analysis during the execution of BBT in a sample of 12 healthy participants with their dominant and non-dominant upper limb. Results revealed that: (i) the BBT can be described by 1 or 2 synergies; the number of synergies (ii) does not differ between dominant and non-dominant sides and (iii) varies considering each phase of the task; (iv) the transfer phase requires more synergies. Clinical Relevance— This preliminary study characterizes muscular synergies during the BBT task in order to establish normative patterns that could assist in understanding the neuromuscular demands and support future evaluations of stroke deficit

The expression and the nuclear activity of the caretaker gene Ku86 are modulated by somatostatin

Somatostatin is a peptide hormone that exerts antisecretory and antiproliferative activities on some human tumors. The Ku70/86 heterodimer acts as regulatory subunit of the DNA dependent protein kinase and its DNA binding activity mediates DNA double strands breaks repair that is crucial to maintain the genetic integrity of the genome. The activation of the heterodimer regulates cell cycle progression and the activity of nuclear transcription factors involved in DNA replication and cell proliferation. Moreover Ku86 behaves as a receptor for the growth inhibitory tetradecapeptide, somatostatin. Herein we report that somatostatin treatment to a colon carcinoma cell line (Caco-2) inhibits cell growth and, at same time, strongly modulates the activation of Ku70/86 heterodimer and the levels of Ku86 in the nucleus by increasing its specific mRNA level. Our findings are consistent with the hypothesis that somatostatin controls cell cycle progression and DNA repair through a new signalling pathway that involves the regulation of Ku86 level and modulates the Ku70/86 activity in the nucleus

i-Motif formation and spontaneous deletions in human cells

Concatemers of d(TCCC) that were first detected through their association with deletions at the RACK7 locus, are widespread throughout the human genome. Circular dichroism spectra show that d(GGGA)n sequences form G-quadruplexes when n > 3, while i-motif structures form at d(TCCC)n sequences at neutral pH when n ≥ 7 in vitro. In the PC3 cell line, deletions are observed only when the d(TCCC)n variant is long enough to form significant levels of unresolved i-motif structure at neutral pH. The presence of an unresolved i-motif at a representative d(TCCC)n element at RACK7 was suggested by experiments showing that that the region containing the d(TCCC)9 element was susceptible to bisulfite attack in native DNA and that d(TCCC)9 oligo formed an i-motif structure at neutral pH. This in turn suggested that that the i-motif present at this site in native DNA must be susceptible to bisulfite mediated deamination even though it is a closed structure. Bisulfite deamination of the i-motif structure in the model oligodeoxynucleotide was confirmed using mass spectrometry analysis. We conclude that while G-quadruplex formation may contribute to spontaneous mutation at these sites, deletions actually require the potential for i-motif to form and remain unresolved at neutral pH