Magnetic graphene oxide nanocarrier for targeted delivery of cisplatin: A perspective for glioblastoma treatment

Selective vectorization of Cisplatin (CisPt) to Glioblastoma U87 cells was exploited by the fabrication of a hybrid nanocarrier composed of magnetic γ-Fe2 O3 nanoparticles and nanographene oxide (NGO). The magnetic component, obtained by annealing magnetite Fe3 O4 and characterized by XRD measurements, was combined with NGO sheets prepared via a modified Hummer’s method. The morphological and thermogravimetric analysis proved the effective binding of γ-Fe2 O3 nanoparticles onto NGO layers. The magnetization measured under magnetic fields up to 7 Tesla at room temperature revealed superparamagnetic-like behavior with a maximum value of MS = 15 emu/g and coercivity HC ≈ 0 Oe within experimental error. The nanohybrid was found to possess high affinity towards CisPt, and a rather slow fractional release profile of 80% after 250 h. Negligible toxicity was observed for empty nanoparticles, while the retainment of CisPt anticancer activity upon loading into the carrier was observed, together with the possibility to spatially control the drug delivery at a target site

Cortical Plasticity Induced by Transcranial Magnetic Stimulation during Wakefulness Affects Electroencephalogram Activity during Sleep

BACKGROUND:Sleep electroencephalogram (EEG) brain oscillations in the low-frequency range show local signs of homeostatic regulation after learning. Such increases and decreases of slow wave activity are limited to the cortical regions involved in specific task performance during wakefulness. Here, we test the hypothesis that reorganization of motor cortex produced by long-term potentiation (LTP) affects EEG activity of this brain area during subsequent sleep. METHODOLOGY/PRINCIPAL FINDINGS:By pairing median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex, one can potentiate the motor output, which is presumed to reflect plasticity of the neural circuitry. This paired associative stimulation increases M1 cortical excitability at interstimulus intervals of 25 ms. We compared the scalp distribution of sleep EEG power following paired associative stimulation at 25 ms to that following a control paradigm with 50 ms intervals. It is shown that the experimental manipulation by paired associative stimulation at 25 ms induces a 48% increase in amplitude of motor evoked potentials. This LTP-like potentiation, induced during waking, affects delta and theta EEG power in both REM and non-REM sleep, measured during the following night. Slow-wave activity increases in some frontal and prefrontal derivations and decreases at sites neighboring and contralateral to the stimulated motor cortex. The magnitude of increased amplitudes of motor evoked potentials by the paired associative stimulation at 25 ms predicts enhancements of slow-wave activity in prefrontal regions. CONCLUSIONS/SIGNIFICANCE:An LTP-like paradigm, presumably inducing increased synaptic strength, leads to changes in local sleep regulation, as indexed by EEG slow-wave activity. Enhancement and depression of slow-wave activity are interpreted in terms of a simultaneous activation of both excitatory and inhibitory circuits consequent to the paired associative stimulation at 25 ms

Sleep in the Human Hippocampus: A Stereo-EEG Study

Background. There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. Methodology/Principal Findings. We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i) a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii) a flattening of the time course of the very low frequencies (up to 1 Hz) across sleep cycles, with relatively high levels of power even during REM sleep; iii) a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. Conclusions/Significance. Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonanc

RISCI - Repeat Induced Sequence Changes Identifier: a comprehensive, comparative genomics-based, in silico subtractive hybridization pipeline to identify repeat induced sequence changes in closely related genomes

<p>Abstract</p> <p>Background -</p> <p>The availability of multiple whole genome sequences has facilitated <it>in silico </it>identification of fixed and polymorphic transposable elements (TE). Whereas polymorphic loci serve as makers for phylogenetic and forensic analysis, fixed species-specific transposon insertions, when compared to orthologous loci in other closely related species, may give insights into their evolutionary significance. Besides, TE insertions are not isolated events and are frequently associated with subtle sequence changes concurrent with insertion or post insertion. These include duplication of target site, 3' and 5' flank transduction, deletion of the target locus, 5' truncation or partial deletion and inversion of the transposon, and post insertion changes like inter or intra element recombination, disruption etc. Although such changes have been studied independently, no automated platform to identify differential transposon insertions and the associated array of sequence changes in genomes of the same or closely related species is available till date. To this end, we have designed RISCI - 'Repeat Induced Sequence Changes Identifier' - a comprehensive, comparative genomics-based, <it>in silico </it>subtractive hybridization pipeline to identify differential transposon insertions and associated sequence changes using specific alignment signatures, which may then be examined for their downstream effects.</p> <p>Results -</p> <p>We showcase the utility of RISCI by comparing full length and truncated L1HS and AluYa5 retrotransposons in the reference human genome with the chimpanzee genome and the alternate human assemblies (Celera and HuRef). Comparison of the reference human genome with alternate human assemblies using RISCI predicts 14 novel polymorphisms in full length L1HS, 24 in truncated L1HS and 140 novel polymorphisms in AluYa5 insertions, besides several insertion and post insertion changes. We present comparison with two previous studies to show that RISCI predictions are broadly in agreement with earlier reports. We also demonstrate its versatility by comparing various strains of <it>Mycobacterium tuberculosis </it>for IS 6100 insertion polymorphism.</p> <p>Conclusions -</p> <p>RISCI combines comparative genomics with subtractive hybridization, inferring changes only when exclusive to one of the two genomes being compared. The pipeline is generic and may be applied to most transposons and to any two or more genomes sharing high sequence similarity. Such comparisons, when performed on a larger scale, may pull out a few critical events, which may have seeded the divergence between the two species under comparison.</p

The Effect of Service on Research Performance: A Study on Italian Academics in Management

Academics all over the world are feeling the increasing pressure to attain satisfactory research performance. Since research is not the only activity required of academics, though, the debate on how it may be coupled with other knowledge transfer activities like teaching, patenting, and dissemination has been captivating scholars interested in higher education. Literature is surprisingly silent about the interplay between research performance and other roles and tasks that faculty are expected to carry out, namely academic citizenship, intended as the service that they provide to their institution, to the scientific community, and to the larger society. Through a negative binomial regression conducted on 692 Italian academics in management, this paper investigates both the direct and moderating effect exerted by academic citizenship on the relationship between research performance in two subsequent evaluation exercises, thus advancing our knowledge of the relationship between research and service. Findings show that institutional service acts as a pure moderator, discipline-based service is a quasi-moderator, while public service exerts only a direct negative effect on research performance. In light of the emergent interplay between research and service, the necessity to boost reflection on academic citizenship is discussed and suggestions for its acknowledgement and advancement are formulated

Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders

Background: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown. Method/Principal Findings: 53 healthy individuals between 18–59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject’s sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 39 untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia. Conclusions: Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brai

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision