Symmetry breaking and strong persistent plasma currents via resonant destabilization of atoms

The ionization rate of an atom in a strong optical field can be resonantly enhanced by the presence of long-living atomic levels (so called Freeman resonances). This process is most prominent in the multiphoton ionization regime meaning that ionization event takes many optical cycles. Nevertheless, here we show that these resonances can lead to fast subcycle-scale plasma buildup at the resonant values of the intensity in the pump pulse. The fast buildup can break the cycletocycle symmetry of the ionization process, resulting in generation of persistent macroscopic plasma currents which remain after the end of the pulse. This, in turn, gives rise to a broadband radiation of unusual spectral structure forming a comb from terahertz (THz) to visible. This radiation contains fingerprints of the attosecond electronic dynamics in Rydberg states during ionization

High binding yet accelerated guest rotation within a cucurbit[7]uril complex. Toward paramagnetic gyroscopes and rolling nanomachines †

International audienceThe (15-oxo-3,7,11-triazadispiro[5.1.5.3]hexadec-7-yl)oxidanyl, a bis-spiropiperidinium nitroxide derived from TEMPONE, can be included in cucurbit[7]uril to form a strong (K a ∼ 2 × 10 5 M −1) CB[7]@bPTO complex. EPR and MS spectra, DFT calculations, and unparalleled increased resistance (a factor of ∼10 3) toward ascorbic acid reduction show evidence of deep inclusion of bPTO inside CB[7]. The unusual shape of the CB[7]@bPTO EPR spectrum can be explained by an anisotropic Brownian rotational diffusion, the global tumbling of the complex being slower than rotation of bPTO around its " long molecular axis " inside CB[7]. The CB[7] (stator) with the encapsulated bPTO (rotator) behaves as a supramolecular para-magnetic rotor with increased rotational speed of the rotator that has great potential for advanced nano-scale machines requiring wheels such as cucurbiturils with virtually no friction between the wheel and the axle for optimum wheel rotation (i.e. nanopulleys and nanocars)

Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress

Protein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e. unfolded protein response (UPR), play key roles in proteostasis but their involvement in the pathology of DMD are largely unknown. Moreover, exercise and activin receptor IIB blocking are two strategies that may be beneficial to DMD muscle, but studies to examine their effects on these proteostasis pathways are lacking. Therefore, these pathways were examined in the muscle of mdx mice, a model of DMD, under basal conditions and in response to seven weeks of voluntary exercise and/or activin receptor IIB ligand blocking using soluble activin receptor-Fc (sAcvR2B-Fc) administration. In conjunction with reduced muscle strength, mdx muscle displayed greater levels of UPR/ER-pathway indicators including greater protein levels of IREloc, PERK and Atf6b mRNA. Downstream to IREloc and PERK, spliced Xbpl mRNA and phosphorylation of elF2oc, were also increased. Most of the cytoplasmic and ER chaperones and mitochondrial UPR markers were unchanged in mdx muscle. Oxidized glutathione was greater in mdx and was associated with increases in lysine acetylated proteome and phosphorylated sirtuin 1. Exercise increased oxidative stress when performed independently or combined with sAcvR2B-Fc administration. Although neither exercise nor sAcvR2B-Fc administration imparted a clear effect on ER stress/UPR pathways or heat shock proteins, sAcvR2B-Fc administration increased protein expression levels of GRP78/BiP, a triggering factor for ER stress/UPR activation and TxNIP, a redox-regulator of ER stress-induced inflammation. In conclusion, the ER stress and UPR are increased in mdx muscle. However, these processes are not distinctly improved by voluntary exercise or blocking activin receptor IIB ligands and thus do not appear to be optimal therapeutic choices for improving proteostasis in DMD. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Prokineticin Receptor-1 Signaling Inhibits Dose- and Time-Dependent Anthracycline-Induced Cardiovascular Toxicity Via Myocardial and Vascular Protection

Abstract Background High prevalence of heart failure during and following cancer treatments remains a subject of intense research and therapeutic interest. Objectives This study investigated how different concentrations of doxorubicin (DOX) can affect the function of the cardiac cells. This study also examined whether activation of prokineticin receptor-1 (PKR1) by a nonpeptide agonist, IS20, prevents DOX-induced cardiovascular toxicity in mouse models. Methods We used cultured cardiomyocytes, endothelial cells (ECs), and epicardium-derived progenitor cells (EPDCs) for in vitro, assays and tumor-bearing and acute and chronic toxicity mouse models for in vivo assays. Results Brief exposure to cardiomyocytes with high-dose DOX increases the accumulation of reactive oxygen species (ROS) by inhibiting a detoxification mechanism via stabilization of cytoplasmic NRF2. Prolonged exposure to medium-dose DOX induces apoptosis in cardiomyocytes, ECs, and EPDCs. However, low-dose DOX promotes functional defects without inducing apoptosis in EPDCs and ECs. IS20 alleviates detrimental effects of DOX in cardiac cells via activating AKT or mitogen-activated protein kinase pathways. Genetic or pharmacological inactivation of PKR1 subdues these effects of IS20. In a chronic mouse model of DOX cardiotoxicity, IS20 normalizes an elevated serum marker of cardiotoxicity and vascular and EPDC deficits, attenuates apoptosis and fibrosis, and improves the survival rate and cardiac function. IS20 does not interfere with the cytotoxicity or antitumor effects of DOX in breast cancer lines or in a mouse model of breast cancer but attenuates the decreases in LV diastolic volume induced by acute DOX treatment. Conclusions This study identifies the molecular and cellular signature of dose-dependent DOX-mediated cardiotoxicity and provides evidence that PKR1 is a promising target to combat cardiotoxicity of cancer treatments

Detection of specific antibodies against toscana virus among blood donors in northeastern Italy and correlation with sand fly abundance in 2014

Toscana virus (TOSV) is a Phlebovirus transmitted by phlebotomine sand flies and is an important etiological agent of summer meningitis in the Mediterranean basin. Since TOSV infection is often asymptomatic, we evaluated the seroprevalence in blood donors (BDs) in the Bologna and Ferrara provinces (Northeastern Italy)\u2014the areas with the highest and lowest numbers of TOSV neuroinvasive cases in the region, respectively. A total of 1208 serum samples from BDs were collected in April\u2013June 2014 and evaluated for the presence of specific TOSV-IgG by ELISA. The IgG-reactive samples were confirmed by indirect immunofluorescence assay (IIF) and by microneutralization test (MN). Serum samples were defined as positive for anti-TOSV IgG when reactive by ELISA and by at least one second-level test; TOSV seroprevalence was 6.8% in the Bologna province, while no circulation of TOSV was detected in the Ferrara province. Sand fly abundance in 2014 was also estimated by a geographic information system using a generalized linear model applied to a series of explanatory variables. TOSV seroprevalence rate was strongly associated with the sand fly abundance index in each municipality, pointing out the strong association between sand fly abundance and human exposure to TOSV

Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

<p>Abstract</p> <p>Background</p> <p>Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.</p> <p>In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study.</p> <p>Results</p> <p>In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p> <p>Conclusions</p> <p>We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p

Lymph node metastasis in grossly apparent clinical stage Ia epithelial ovarian cancer: Hacettepe experience and review of literature

Background Lymphadenectomy is an integral part of the staging system of epithelial ovarian cancer. However, the extent of lymphadenectomy in the early stages of ovarian cancer is controversial. The objective of this study was to identify the lymph node involvement in unilateral epithelial ovarian cancer apparently confined to the one ovary (clinical stage Ia). Methods A prospective study of clinical stage I ovarian cancer patients is presented. Patient's characteristics and tumor histopathology were the variables evaluated. Results Thirty three ovarian cancer patients with intact ovarian capsule were evaluated. Intraoperatively, neither of the patients had surface involvement, adhesions, ascites or palpable lymph nodes (supposed to be clinical stage Ia). The mean age of the study group was 55.3 ± 11.8. All patients were surgically staged and have undergone a systematic pelvic and paraaortic lymphadenectomy. Final surgicopathologic reports revealed capsular involvement in seven patients (21.2%), contralateral ovarian involvement in two (6%) and omental metastasis in one (3%) patient. There were two patients (6%) with lymph node involvement. One of the two lymph node metastasis was solely in paraaortic node and the other metastasis was in ipsilateral pelvic lymph node. Ovarian capsule was intact in all of the patients with lymph node involvement and the tumor was grade 3. Conclusion In clinical stage Ia ovarian cancer patients, there may be a risk of paraaortic and pelvic lymph node metastasis. Further studies with larger sample size are needed for an exact conclusion.PubMedWoSScopu

Circadian rest-activity rhythm as an objective biomarker of patient-reported outcomes in patients with advanced cancer

Background Psychosocial symptoms often cluster together, are refractory to treatment, and impair health‐related quality of life (HR‐QoL) in cancer patients. The contribution of circadian rhythm alterations to systemic symptoms has been overlooked in cancer, despite a causal link shown under jet lag and shift work conditions. We investigated whether the circadian rest‐activity rhythm provides a reliable and objective estimate of the most frequent patient‐reported outcome measures (PROMs). Methods Two datasets were used, each involving concomitant 3‐day time series of wrist actigraphy and HR‐QoL questionnaires: EORTC QLQ‐C30 was completed once by 237 patients with metastatic colorectal cancer; MD Anderson Symptom Inventory (MDASI) was completed daily by 31 patients with advanced cancer on continuous actigraphy monitoring, providing 1015 paired data points. Circadian function was assessed using the clinically validated dichotomy index I < O. Nonparametric tests compared PROMs and I < O. Effect sizes were computed. Sensitivity subgroup and temporal dynamics analyses were also performed. Results I < O values were significantly lower with increasing symptom severity and worsening HR‐QoL domains. Fatigue and anorexia were worse in patients with circadian disruption. The differences were both statistically and clinically significant (P < 0.001; d ≥ 0.33). Physical and social functioning, and global quality/enjoyment of life were significantly better in patients with robust circadian rhythm (P < 0.001; d ≥ 0.26). Sensitivity analyses validated these findings. Conclusion Objectively determined circadian disruption was consistently and robustly associated with clinically meaningfully severe fatigue, anorexia, and interference with physical and social functioning. This supports an important role of the circadian system in the determination of cancer patients’ HR‐QoL and symptoms that deserves therapeutic exploitation