Multilobar electrocorticography monitoring during intracranial aneurysm surgery

Introduction: To detect a neuronal threshold of tolerance to ischemia, the usefulness of multilobar electrocorticography (mEcoG) during intracranial aneurysm surgery was compared to the scalp EEG and correlated with the postoperative neurological status and the radiological findings. Methods: Twenty-one patients harboring intracranial aneurysms were monitored by simultaneous scalp EEG and lobe-dependent mEcoG during surgical clipping. The patients were divided into group A (6 patients with no temporary clipping) and group B (15 patients with temporary clipping). Results: New focal modifications of the mEcoG signal with high frequency (HF)-β3 and delta waves were observed in none of the patients in group A and all of the patients in group B. These anomalies were followed by focal burst suppression pattern in eight cases (53%) in group B. These changes were detected in only two cases (9%) on the scalp EEG. New corticographic changes resolved in eight patients (53%) in group B. Among the seven patients in group B who had persistent focal burst pattern after clip removal, six (85%) presented with new neurological deficit or new hypodensity on CT. The Glasgow Outcome Scale was good (IV or V) in 85% of cases. Conclusion: mEcoG is more sensitive than scalp EEG. The appearance and persistence of the focal burst suppression pattern shown on mEcoG, was associated with a new neurological deficit or new hypodensity, whereas HF-β3 or delta waves per se were not associated with new changes. A better comprehension of these EEG anomalies could determine the duration of temporary clipping and consequently influence the surgical strateg

Updating the mechanisms of common fragile site instability: how to reconcile the different views?

Common fragile sites (CFSs) are large chromosomal regions long identified by conventional cytogenetics as sequences prone to breakage in cells subjected to replication stress. The interest in CFSs came from their key role in the formation of DNA damage, resulting in chromosomal rearrangements. The instability of CFSs was notably correlated with the appearance of genome instability in precancerous lesions and during tumor progression. Identification of the molecular mechanisms responsible for their instability therefore represents a major challenge. A number of data show that breaks result from mitotic entry before replication completion but the mechanisms responsible for such delayed replication of CFSs and relaxed checkpoint surveillance are still debated. In addition, clues to the molecular events leading to breakage just start to emerge. We present here the results of recent reports addressing these questions

Amplicon rearrangements during the extrachromosomal and intrachromosomal amplification process in a glioma

International audienceThe mechanisms of gene amplification in tumour cells are poorly understood and the relationship between extrachromosomal DNA molecules, named double minutes (dmins), and intrachromosomal homogeneously staining regions (hsr) is not documented at nucleotide resolution. Using fluorescent in situ hybridization and whole genome sequencing, we studied a xenografted human oligodendroglioma where the co-amplification of the EGFR and MYC loci was present in the form of dmins at early passages and of an hsr at later passages. The amplified regions underwent multiple rearrangements and deletions during the formation of the dmins and their transformation into hsr. In both forms of amplification, non-homologous end-joining and microhomology-mediated end-joining rather than replication repair mechanisms prevailed in fusions. Small fragments, some of a few tens of base pairs, were associated in contigs. They came from clusters of breakpoints localized hundreds of kilobases apart in the amplified regions. The characteristics of some pairs of junctions suggest that at least some fragments were not fused randomly but could result from the concomi-tant repair of neighbouring breakpoints during the interaction of remote DNA sequences. This characterization at nucleotide resolution of the transition between extra-and intrachromosome amplifications highlights a hitherto uncharacterized organization of the amplified regions suggesting the involvement of new mechanisms in their formation

Assessment of mental workload: A new electrophysiological method based on intra-block averaging of ERP amplitudes

The present study contributes to the current debate about electrophysiological measurements of mental workload. Specifically, the allocation of attentional resources during different complexity levels of tasks and its changes over time are of great interest. Therefore, we investigated mental workload using tasks varying in difficulty during an auditory oddball target paradigm. For data analysis, we applied a novel method to compute event-related potentials (ERPs) by intra-block epoch averaging of P2, P3a and P3b amplitude components for the infrequent target stimuli. We obtained eight consecutive blocks of 5 epochs each, which allowed us to develop an electrophysiological parameter to measure mental workload. In both the easy and the more constraining tasks, the amplitude of P2 decreased beginning with the second block of the sequence. In contrast, the amplitudes of P3a and P3b components linearly decreased following the repetition of the target in the more constraining task, but not in the easy task. Statistical analysis revealed intra-block differences on amplitudes of ERPs of interest between the easy and the more constraining tasks, confirming this method as a measure to assess mental workload. Since a subject is his own control, the present method represents an electrophysiological parameter for individual measurement of mental workload and may therefore be applicable in clinical routine

Allocation dans le temps des produits agricoles: comparaison entre le système des majorations mensuelles communautaire et celui de la mise à prix de l'espace de stockage sur les marchés à terme

The intervention policy on the EEC grain market is completed by a system of monthly increments designed to level the sales of grain all over the year. The efficiency of this organisation is compared with the price formation over time on futures markets

Centrosome clustering and Cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors

Background: Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Methods: Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed. Results: Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Conclusions: Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001)

Job Exposure Matrix, a Solution for Retrospective Assessment of Particle Exposure in a Subway Network and Their Long-Term Effects.

Health effects after long-term exposure to subway particulate matter (PM) remain unknown due to the lack of individual PM exposure data. This study aimed to apply the job exposure matrix (JEM) approach to retrospectively assess occupational exposure to PM in the Parisian subway. Job, the line and sector of the transport network, as well as calendar period were four JEM dimensions. For each combination of these dimensions, we generated statistical models to estimate the annual average PM &lt;sub&gt;10&lt;/sub&gt; concentration using data from an exhaustive inventory of the PM measurement campaigns conducted between 2004 and 2020 in the Parisian subway and historical data from the Parisian air pollution monitoring network. The resulting JEM and its exposure estimates were critically examined by experts using the uncertainty analysis framework. The resulting JEM allows for the assignment of the estimated annual PM &lt;sub&gt;10&lt;/sub&gt; concentration to three types of professionals working in the subway: locomotive operators, station agents, and security guards. The estimates' precision and validity depend on the amount and quality of PM &lt;sub&gt;10&lt;/sub&gt; measurement data used in the job-, line-, and sector-specific models. Models using large amounts of personal exposure measurement data produced rather robust exposure estimates compared to models with lacunary data (i.e., in security guards). The analysis of uncertainty around the exposure estimates allows for the identification of the sources of uncertainty and parameters to be addressed in the future in order to refine and/or improve the JEM. The JEM approach seems relevant for the retrospective exposure assessment of subway workers. When applied to available data on PM &lt;sub&gt;10&lt;/sub&gt; , it allows for the estimation of this exposure in locomotive operators and station agents with an acceptable validity. Conversely, for security guards, the current estimates have insufficient validity to recommend their use in an epidemiological study. Therefore, the current JEM should be considered as a valid prototype, which shall be further improved using more robust measurements for some jobs. This JEM can also be further refined by considering additional exposure determinants

Metal and oxidative potential exposure through particle inhalation and oxidative stress biomarkers: a 2-week pilot prospective study among Parisian subway workers.

In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field. We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2'deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times. The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDA &lt;sub&gt;EBC&lt;/sub&gt; generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day. Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter

USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication

DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during G1 and G1/S phases of the cell cycle. USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. In addition, downregulation of USP37 reduces DNA replication fork speed. Taken together, here we show that the deubiquitinase USP37 plays an important role in the regulation of DNA replication. Whether this is achieved via Cdt1, a central protein in this process, which we have shown to be stabilized by USP37, or via additional factors, remains to be tested.The authors are grateful to V. Smits for careful reading of the manuscript. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2013-49149-R, BFU2014-51672-REDC), Instituto de Salud Carlos III (BA15/00092) and Fundacion CajaCanarias (AP2015/008) to RF.S