Influence of supramolecular forces on the linear viscoelasticity of gluten

Stress relaxation behavior of hydrated gluten networks was investigated by means of rheometry combined with μ-computed tomography (μ-CT) imaging. Stress relaxation behavior was followed over a wide temperature range (0–70 °C). Modulation of intermolecular bonds was achieved with urea or ascorbic acid in an effort to elucidate the presiding intermolecular interactions over gluten network relaxation. Master curves of viscoelasticity were constructed, and relaxation spectra were computed revealing three relaxation regimes for all samples. Relaxation commences with a well-defined short-time regime where Rouse-like modes dominate, followed by a power law region displaying continuous relaxation concluding in a terminal zone. In the latter zone, poroelastic relaxation due to water migration in the nanoporous structure of the network also contributes to the stress relief in the material. Hydrogen bonding between adjacent protein chains was identified as the determinant force that influences the relaxation of the networks. Changes in intermolecular interactions also resulted in changes in microstructure of the material that was also linked to the relaxation behavior of the networks

Autophagy in healthy aging and disease

Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health

Device-related infection in de novo transvenous implantable cardioverter-defibrillator Medicare patients

BACKGROUND: Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection. OBJECTIVE: To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population. METHODS: A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (7/2016-12/2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a p≤0.25 for inclusion in a multivariable model and a backwards, stepwise elimination process with p≤0.1 to remain in the model. A time-to-event analysis was also conducted. RESULTS: Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post-implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus. CONCLUSION: The rate of de novo TV-ICD infection was 1.9% and identified risk factors associated with infection may be useful in device selection

Fulvestrant-induced expression of ErbB3 and ErbB4 receptors sensitizes oestrogen receptor-positive breast cancer cells to heregulin β1

Introduction We have previously reported that induction of epidermal growth factor receptor and ErbB2 in response to antihormonal agents may provide an early mechanism to allow breast cancer cells to evade the growth-inhibitory action of such therapies and ultimately drive resistant cell growth. More recently, the other two members of the ErbB receptor family, ErbB3 and ErbB4, have been implicated in antihormone resistance in breast cancer. In the present study, we have investigated whether induction of ErbB3 and/or ErbB4 may provide an alternative resistance mechanism to antihormonal action in a panel of four oestrogen receptor (ER)-positive breast cancer cell lines. Methods MCF-7, T47D, BT474 and MDAMB361 cell lines were exposed to fulvestrant (100 nM) for seven days, and effects on ErbB3/4 expression and signalling, as well as on cell growth, were assessed. Effects of heregulin β1 (HRGβ1) were also examined in the absence and presence of fulvestrant to determine the impact of ER blockade on the capacity of this ErbB3/4 ligand to promote signalling and cell proliferation. Results Fulvestrant potently reduced ER expression and transcriptional activity and significantly inhibited growth in MCF-7, T47D, BT474 and MDAMB361 cells. However, alongside this inhibitory activity, fulvestrant also consistently induced protein expression and activity of ErbB3 in MCF-7 and T47D cells and ErbB4 in BT474 and MDAMB361 cell lines. Consequently, fulvestrant treatment sensitised all cell lines to the actions of the ErbB3/4 ligand HRGβ1 with enhanced ErbB3/4-driven signalling activity, reexpression of cyclin D1 and significant increases in cell proliferation being observed when compared to untreated cells. Indeed, in T47D and MDAMB361 HRGβ1 was converted from a ligand having negligible or suppressive growth activity into one that potently promoted cell proliferation. Consequently, fulvestrant-mediated growth inhibition was completely overridden by HRGβ1 in all four cell lines. Conclusions These findings suggest that although antihormones such as fulvestrant may have potent acute growth-inhibitory activity in ER-positive breast cancer cells, their ability to induce and sensitise cells to growth factors may serve to reduce and ultimately limit their inhibitory activity

Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

The carcinoma in situ (CIS) cell is the common precursor of nearly all testicular germ cell tumours (TGCT). In a previous study, we examined the gene expression profile of CIS cells and found many features common to embryonic stem cells indicating that initiation of neoplastic transformation into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM and a sample containing a mixture of N-SEM components, and analyse the data together with the previously published data on CIS. Genes showing expression in the SEM or N-SEM were selected, in order to identify gene expression markers associated with the progression of CIS cells. The identified markers were verified by reverse transcriptase–polymerase chain reaction and in situ hybridisation in a range of different TGCT samples. Verification showed some interpatient variation, but combined analysis of a range of the identified markers may discriminate TGCT samples as SEMs or N-SEMs. Of particular interest, we found that both DNMT3B (DNA (cytosine-5-)-methyltransferase 3 beta) and DNMT3L (DNA (cytosine-5-)-methyltransferase 3 like) were overexpressed in the N-SEMs, indicating the epigenetic differences between N-SEMs and classical SEM

Radiating Shear-Free Gravitational Collapse with Charge

We present a new shear free model for the gravitational collapse of a spherically symmetric charged body. We propose a dissipative contraction with radiation emitted outwards. The Einstein field equations, using the junction conditions and an ansatz, are integrated numerically. A check of the energy conditions is also performed. We obtain that the charge delays the black hole formation and it can even halt the collapse.Comment: 22 pages, 9 figures. It has been corrected several typos and included several references. Accepted for publication in GR

Carotid bruits as predictor for carotid stenoses detected by ultrasonography: an observational study

<p>Abstract</p> <p>Background</p> <p>Carotid surgery in asymptomatic subjects with carotid stenosis is effective to prevent ischemic stroke. There is, however, uncertainty how to find such persons at risk, because mass screening with carotid artery ultrasonography (US) is not cost-effective. Signs of carotid bruits corresponding to the carotid arteries may serve as a tool to select subjects for further investigation. This study is thus aimed at determining the usefulness of carotid bruits in the screening of carotid stenoses.</p> <p>Methods</p> <p>1555 consecutive carotid ultrasonography investigations from 1486 cases done between January 2004 and March 2006 at Norrlands University Hospital, Sweden, were examined. 356 subjects, medium age 69 (27–88) years, had a significant (≥ 50%) US-verified carotid stenosis uni- or bilaterally, 291 had been examined for signs of carotid bruits. The likelihood ratios for carotid bruits to predict US-verified carotid stenoses were calculated and expressed as likelihood percentages.</p> <p>Results</p> <p>Thirty-one out of 100 persons (31%) with carotid bruit as an indication to perform carotid US had a significant (≥ 50%) carotid stenosis. 281 of the 356 (79%) cases with significant carotid stenoses were found among patients with cerebrovascular disease (CVD). 145 of 226 (64%) CVD patients with a significant carotid stenosis had a carotid bruit. In patients with 50–99% carotid stenoses carotid bruits had an accuracy of 75% (436/582), a sensitivity of 71% (236/334), a specificity of 81% (200/248), a positive likelihood ratio at 3.65 and a negative likelihood at 0.36. Patients with 70–99% stenoses had the highest sensitivity at 77% (183/238). In patients with 100% carotid stenoses, carotid bruits had a sensitivity of 26% (15/57) and a specificity of 49% (256/525).</p> <p>Conclusion</p> <p>Although carotid bruits are not accurate to confirm or to exclude significant carotid stenoses, these signs are appropriate for directed screening for further investigation with carotid US if the patient lacks contraindications for surgery. Lack of carotid bruits in CVD patients does not exclude a carotid stenosis.</p

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet