Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the ...atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress.
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•Endothelial cells dysfunction is critical in the process of atherothrombosis.•Endoplasmic reticulum stress is a key component in endothelial cell dysfunction.•Oxysterols are oxidation products of cholesterol found in atherosclerosis lesions.•Oxysterols are potential modulators of endoplasmic reticulum stress.
Background and purpose
We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour‐related epilepsy ...(BTRE).
Methods
This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test‐12 questionnaire at baseline and after 5 months.
Results
Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non‐neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs.
Conclusions
Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first‐line option in patients with BTRE because of easy titration and few significant drug‐to‐drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.
Objective
To evaluate partial HPV16/18 genotyping as a possible biomarker to select women attending HPV‐based cervical cancer screening at higher risk to be referred to colposcopy.
Design
...Population‐based cohort study.
Setting
Organised cervical cancer screening programmes (Italy).
Population
Women with high‐risk HPV infection (period: 2015–2019).
Methods
We analysed the association between partial HPV16/18 genotyping, cytology triage and histologically confirmed diagnosis of high‐grade cervical intraepithelial neoplasia (CIN3+) lesions.
Main outcome measures
Detection rate (DR) and positive predictive value (PPV) for histologically confirmed CIN3+ (any episode in the 2 years after baseline); sensitivity for CIN3+ and number of colposcopies needed for lesion detection.
Results
The study included 145 437 women screened with HPV testing by the clinically validated COBAS 4800 HPV assay (Roche). Overall, 9601 (6.6%) women were HPV+ at baseline; HPV16 and HPV18 were present in 1865 and 594 samples, respectively. The cumulative (baseline plus 1‐year repeat) cytology positivity was 42.8% and high‐grade cytology was significantly higher (P < 0.0001) among women with HPV16 infection at baseline (15.2%). The cumulative CIN3+ DR for women with HPV16, HPV18 and other HPV‐type infections was 9.8%, 3.4% and 1.8%, respectively.
Conclusions
Partial HPV16 genotyping may play a role in triage, whereas HPV18 seems to behave much more similarly to the other HPV types and does not provide additional stratification. HPV16 genotyping combined with high‐grade cytology can be envisaged as a triage biomarker in cervical screening to maximise CIN3+ detection while minimising colposcopy at baseline or 1‐year repeat.
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HPV16 genotyping combined with high‐grade cytology can be used as triage biomarker for CIN3+ in HPV‐positive women.
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HPV16 genotyping combined with high‐grade cytology can be used as a triage biomarker for CIN3+ in HPV‐positive women.
On September 14th 2015 the first gravitational wave signal has been detected by the Advanced LIGO interferometers, opening the era of the gravitational astronomy and giving new opportunities to ...investigate the universe. The Advanced LIGO and Advanced Virgo interferometers are now back in a commissioning phase in order to improve their sensitivity for the next observing run, which will start in the first months of 2019. In the high-frequencies region of their sensitivity band, the detectors are shot-noise limited: the sensitivity in this frequency window could be improved increasing the laser input power, but this increases also the optical aberrations due to the thermal effects. The optical power absorptions in the substrate and coatings of the optics induce both an increase of the optical path length in the substrates of the mirrors (thermal lensing) and a thermal expansion of the optic itself along the optical axis (thermo-elastic deformation). Both these aberrations reduce the sensitivity of the detector, limiting its performances. In order to face and minimize them, an adaptive Thermal Compensation System is required in order to guarantee the proper operation of the interferometer. An overview of the present Thermal Compensation System system installed on Advanced Virgo, with also a focus on the possible improvements of the actual actuators for the next generation of detectors, is presented here.
Nuclear lamins are the main components of the nuclear lamina at the nuclear periphery, providing mechanical support to the nucleus. However, recent findings suggest that lamins also reside in the ...nuclear interior, as a distinct and dynamic pool with critical roles in transcriptional regulation. In our work we found a functional and evolutionary conserved crosstalk between Lamin A/C and the Polycomb group (PcG) of proteins, this being required for the maintenance of the PcG repressive functions. Indeed, Lamin A/C knock-down causes PcG foci dispersion and defects in PcG-mediated higher order structures, thereby leading to impaired PcG mediated transcriptional repression. By using ad-hoc algorithms for image analysis and PLA approaches we hereby show that PcG proteins are preferentially located in the nuclear interior where they interact with nucleoplasmic Lamin A/C. Taken together, our findings suggest that nuclear components, such as Lamin A/C, functionally interact with epigenetic factors to ensure the correct transcriptional program maintenance.
Microscopy techniques have been widely applied to observe cellular ultrastructure. Most of these techniques, such as transmission electron microscopy, produce high‐resolution images, but they may ...require extensive preparation, hampering their application for in vivo examination. Other approaches, such as fluorescent and fluorogenic probes, can be applied not only to fixed specimens but also to living cells when the probes are nontoxic. Fluorescence‐based methods, which are generally relatively easy to use, allow visual and (semi)quantitative studies of the ultrastructural organization and processes of the cell under natural as well as manipulated conditions. To date, there are relatively few published studies on the nearly ubiquitous marine protistan group Foraminifera that have used fluorescent and fluorogenic probes, despite their huge potential. The aim of the present contribution is to document the feasible application of a wide array of these probes to foraminiferal biology. More specifically, we applied fluorescence‐based probes to study esterase activity, cell viability, calcium signaling, pH variation, reactive oxygen species, neutral and polar lipids, lipid droplets, cytoskeleton structures, Golgi complex, acidic vesicles, nuclei, and mitochondria in selected foraminiferal species.
Key Points
Fluorescence imaging facilitates the understanding of biological processes
Fluorescent and fluorogenic probes can be applied to foraminifera
Fluorescence‐based methods are powerful techniques to visualize certain ultrastructural organization of foraminiferal cells
Campylobacter jejuni
is the most common cause of bacterial gastroenteritis in humans. The synthesis of cytolethal distending toxin appears essential in the infection process. In this work we ...evaluated the sequence of lethal events in HeLa cells exposed to cell lysates of two distinct strains,
C. jejuni
ATCC 33291 and
C. jejuni
ISS3.
C. jejuni
cell lysates (CCLys) were added to HeLa cell monolayers which were analysed to detect DNA content, death features, bcl-2 and p53 status, mitochondria/lysosomes network and finally, CD54 and CD59 alterations, compared to cell lysates of
C. jejuni
11168H
cdt
A mutant. We found mitochondria and lysosomes differently targeted by these bacterial lysates. Death, consistent with apoptosis for
C. jejuni
ATCC 33291 lysate, occurred in a slow way (>48 h); concomitantly HeLa cells increase their endolysosomal compartment, as a consequence of toxin internalization besides a simultaneous and partial lysosomal destabilization.
C. jejuni
CCLys induces death in HeLa cells mainly via a caspase-dependent mechanism although a p53 lysosomal pathway (also caspase-independent) seems to appear in addition. In
C. jejuni
ISS3-treated cells, the p53-mediated oxidative degradation of mitochondrial components seems to be lost, inducing the deepest lysosomal alterations. Furthermore, CD59 considerably decreases, suggesting both a degradation or internalisation pathway. CCLys-treated HeLa cells increase CD54 expression on their surface, because of the action of lysate as its double feature of toxin and bacterial peptide. In conclusion, we revealed that
C. jejuni
CCLys-treated HeLa cells displayed different features, depending on the particular strain.
The thermal noise coupling with the displacement of the mirrors of a gravitational wave interferometric detector is a limit to its sensitivity in a range of frequencies from about 10
Hz to few ...hundreds of Hz; fused silica proved to be a very suitable material to reduce this source of noise for the first generation of detectors. The future advanced detectors are planning to make use of fused silica mirrors and suspending elements in a monolithic arrangement: in these conditions, the main contribution to the thermal noise will come from the amorphous multilayered coating deposited on the mirrors. This paper is focused on the multiple advantages provided by the use of fused silica material in a present day interferometric detector; a new suspension for measurements of the acoustic attenuation in fused silica is presented together with the loss angle dependance on frequency and aspect ratio. Furthermore we report on the status of the art of the research activity on fused silica wires production and characterization and coating thermal noise accomplished by the Firenze–Urbino Virgo group.
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