bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between prostate cancer cells and prostate fibroblasts promotes accumulation and proteolytic processing of basement membrane proteins
Authors: Ojalill Marjaana , Virtanen Noora , Rappu Pekka , Siljamäki Elina , Taimen Pekka , Heino Jyrki
Published: May 2020

Background

Tumor microenvironment or stroma has the potency to regulate the behavior of malignant cells. Fibroblast‐like cells are abundant in tumor stroma and they are also responsible for the synthesis of many extracellular matrix components. Fibroblast‐cancer cell interplay can modify the functions of both cell types.

Methods

We applied mass spectrometry and proteomics to unveil the matrisome in 3D spheroids formed by DU145 prostate cancer cells, PC3 prostate cancer cells, or prostate‐derived fibroblasts. Similarly, DU145/fibroblast and PC3/fibroblast coculture spheroids were also analyzed. Western blot analysis and immunofluorescence were used to confirm the presence of specific proteins in spheroids. Cancer dissemination was studied by utilizing “out of spheroids” migration and invasion assays.

Results

In the spheroid model cancer cell‐fibroblast interplay caused remarkable changes in the extracellular matrix and accelerated the invasion of DU145 cells. Fibroblasts produced structural matrix proteins, growth factors, and matrix metalloproteinases. In cancer cell/fibroblast cocultures basement membrane components, including laminins (α3, α5, β2, and β3), heparan sulfate proteoglycan (HSPG2 gene product), and collagen XVIII accumulated in a prominent manner when compared with spheroids that contained fibroblasts or cancer cells only. Furthermore, collagen XVIII was intensively processed to different endostatin‐containing isoforms by cancer cell‐derived cathepsin L.

Conclusions

Fibroblasts can promote carcinoma cell dissemination by several different mechanisms. Extracellular matrix and basement membrane proteins provide attachment sites for cell locomotion promoting adhesion receptors. Growth factors and metalloproteinases are known to accelerate cell invasion. In addition, cancer cell‐fibroblast interplay generates biologically active fragments of basement membrane proteins, such as endostatin.
Optically Black and Electrically Insulating Ag–Fe–O‐Based Thin Films for Touch Panel Displays
Authors: Ishii Akihiro , Yamaguchi Mina , Oikawa Itaru , Yamazaki Yusuke , Imura Masaaki , Kanai Toshimasa , Takamura Hitoshi
Published: May 2020

Apart from transparent conductors, the demand for nontransparent black insulators in the electronic display industry is significant. The development of these dark insulators requires sophisticated material designs. This study shows that narrow‐gap‐oxide‐based nanoscale cermets with nonequilibrium phases which decompose into metal and oxide phases have both the insulative character and a stronger and less‐dispersive absorption than graphite throughout the visible range. Herein, the cases of pulsed‐laser‐deposition‐derived Ag–Fe2O3 and Cu–Bi2O3 systems are shown. The combination of the interband absorption of the narrow‐gap oxides and the plasmonic absorption of the metals provides strong optical absorption throughout the visible range. Because they create diffusion at the edge of the interband absorption and the peaks of the plasmonic absorption, the nonequilibrium phases make the absorption less dispersive. By preventing the mutual contact of the metal grains, they also make the cermets electrically insulative. This new approach has the potential to produce excellent black and insulating optical coatings using a variety of combinations of metals and ceramics for touch panel displays.
The effect of synbiotic supplementation on anthropometric indices, appetite, and constipation in people with hypothyroidism: A randomized, double‐blind, placebo‐controlled trial
Authors: Talebi Sepide , Karimifar Mozhgan , Heidari Zahra , Mohammadi Hamed , Asbaghi Omid , Hadi Amir , Marx Wolfgang , Askari Gholamreza
Published: May 2020

Abstarct

Hypothyroidism and obesity are two highly prevalent conditions that appear to be closely related. Hypothyroidism is correlated with weight gain, loss of appetite, constipation, and a higher incidence of obesity. The present study aimed to investigate the effects of synbiotic supplementation on anthropometric indices, appetite, and constipation in subjects with hypothyroidism. Sixty subjects with hypothyroidism were assigned into two groups to receive either 500 mg/day of synbiotic (n = 30) or a placebo (n = 30) per day for 8 weeks. Anthropometric indices, appetite, and constipation were assessed at study baseline and end of the trial. At the end of trial, waist‐to‐hip ratio was significantly decreased in the synbiotic group (p = .030), whereas there were no significant differences between groups. We did not observe any statistically significant change in appetite or other anthropometric indices (p > .05). Compared with the placebo synbiotic supplementation led to a significant reduction in constipation (p = .048). The results of the present trial indicated that synbiotic supplementation may have favorable results in constipation among subjects with hypothyroidism for 8 weeks. Further studies with larger sample size and longer duration are needed to confirm our findings.
Assessing the potential and application of crowdsourced urban wind data
Authors: Droste Arjan M. , Heusinkveld Bert G. , Fenner Daniel , Steeneveld Gert‐Jan
Published: May 2020

The use of crowdsourcing – obtaining large quantities of data through the Internet – has been of great value in urban meteorology. Crowdsourcing has been used to obtain urban air temperature, air pressure, and precipitation data from sources such as mobile phones or personal weather stations (PWSs), but so far wind data have not been researched. Urban wind behaviour is highly variable and challenging to measure, since observations strongly depend on the location and instrumental set‐up. Crowdsourcing can provide a dense network of wind observations and may give insight into the spatial pattern of urban wind. In this study, we evaluate the skill of the popular “Netatmo” PWS anemometer against a reference for a rural and an urban site. Subsequently, we use crowdsourced wind speed observations from 60 PWSs in Amsterdam, the Netherlands, to analyse wind speed distributions of different Local Climate Zones (LCZs). The Netatmo PWS anemometer appears to systematically underestimate the wind speed, and episodes with rain or high relative humidity degrade the measurement quality. Therefore, we developed a quality assurance (QA) protocol to correct PWS measurements for these errors. The applied QA protocol strongly improves PWS data to a point where they can be used to infer the probability density distribution of wind speed of a city or neighbourhood. This density distribution consists of a combination of two Weibull distributions, rather than the typical single Weibull distribution used for rural wind speed observations. The limited capability of the Netatmo PWS anemometer to measure near‐zero wind speed causes the QA protocol to perform poorly for periods with very low wind speeds. However, results for a year‐long wind speed climatology of the wind speed are satisfactory, as well as for a shorter period with higher wind speeds.
Statistical properties of minimal sufficient balance and minimization as methods for controlling baseline covariate imbalance at the design stage of sequential clinical trials
Authors: Lauzon Steven D. , Ramakrishnan Viswanathan , Nietert Paul J. , Ciolino Jody D. , Hill Michael D. , Zhao Wenle
Published: May 2020

When the number of baseline covariates whose imbalance needs to be controlled in a sequential randomized controlled trial is large, minimization is the most commonly used method for randomizing treatment assignments. The lack of allocation randomness associated with the minimization method has been the source of controversy, and the need to reduce even minor imbalances inherent in the minimization method has been challenged. The minimal sufficient balance (MSB) method is an alternative to the minimization method. It prevents serious imbalance from a large number of covariates while maintaining a high level of allocation randomness. In this study, the two treatment allocation methods are compared with regards to the effectiveness of balancing covariates across treatment arms and allocation randomness in equal allocation clinical trials. The MSB method proves to be equal or superior in both respects. In addition, type I error rate is preserved in analyses for both balancing methods, when using a binary endpoint.
Dendrimer with Interior Cavity as Catalytic Pockets for Substrate Molecules: Synthesis of Bisimidazoles and Molecular Docking Study
Authors: Baby Sherlymole Parackal , Ronaldo Anuf Alexander , Anjali Krishna Gopalakrishnan , Sreekumar Krishnapillai
Published: May 2020

Dendritic nanostructure with the catalytic moiety covalently attached within the core domain and protected from the environment by a polymeric shell was synthesized successfully. This prospective will focus on the exclusive features observed for such a catalytic system with reactive sites present both at the core and the periphery and highlight its potential as enzyme mimics, by synthesizing different bisimidazoles following the MCR method, at room temperature. An unprecedented reaction rate and high yield of products were obtained within a short time, which is supposed to be its ability to form reverse micelle in the core, where the substrates are adequately concentrated. This is the first reported synthesis of bisimidazoles, using the homogeneous PAMAM dendrimer as a basic organocatalyst. The newly synthesized bisimidazoles obtained from bis(3‐aminopropyl)amine were subjected to molecular docking studies against anticancer protein receptor using AutoDock Vina software, to evaluate their activity against breast cancer cell line (3HB5).
Asymmetric Synthesis of Methyl Specifically Labelled L‐Threonine and Application to the NMR Studies of High Molecular Weight Proteins
Authors: Ayala Isabel , Chiari Lucile , Kerfah Rime , Boisbouvier Jerome , Gans Pierre , Hamelin Olivier
Published: May 2020

Methyl groups are valuable probes for solution NMR, allowing the investigation of large protein complexes. Among the six methyl containing residues, threonine has one of the less hydrophobic side chain, and can reside both within the interior of a protein or on the protein surface. This article presents an efficient mixed chemical/enzymatic synthesis scheme, enabling the preparation of threonine with natural configuration on the two stereogenic centers together with an optimal introduction of 1H/2H and 12C/13C atoms at specific sites. Such specifically labelled amino acid can be efficiently incorporated in overexpressed proteins without scrambling or in combination with any other types of 13CH3 probes. Additionally we report application to the 82 kDa Malate Synthase G. Our findings demonstrate that structural meaningful long range nOes can be detected between threonine methyl probes and methionine and isoleucine methyl groups distant by 12 Å.
Biomimetic Engineering of a Scavenger‐Free Nitric Oxide‐Generating/Delivering System to Enhance Radiation Therapy
Authors: Lin Yu‐Jung , Chen Chun‐Chieh , Nguyen Dang , Su Huei‐Rou , Lin Kun‐Ju , Chen Hsin‐Lung , Hu Yu‐Jung , Lai Po‐Liang , Sung Hsing‐Wen
Published: May 2020

Nitric oxide (NO) is a potent tumor‐cell radiosensitizer but it can be readily scavenged by hemoglobin (Hb) in vivo. A biomimetic incubator that can generate and deliver NO in a scavenger (Hb)‐free environment to enhance its radiosensitizing effect to maximize its efficacy in radiotherapy is proposed. This NO incubator comprises a poly(lactic‐co‐glycolic acid) (PLGA) hollow microsphere (HM) that contains an NO donor (NONOate) and a surfactant molecule (sodium caprate, SC) in its aqueous core. In acidic tumorous environments, the PLGA shell of the HM allows the penetration of protons from the outside, activating the hydrolytic cleavage of NONOate, spontaneously generating NO bubbles, which are immediately trapped/stabilized by SC. The SC‐stabilized NO bubbles in the HM are then squeezed through the spaces of its PLGA matrices by the elevated internal pressure. Upon leaving the HM, the entrapped NO molecules may passively diffuse through their SC‐stabilized/protected layer gradually to the tumor site, having a long‐lasting radiosensitizing effect and inhibiting tumor growth. The entire process of NO generation and delivery is conducted in a scavenger (Hb)‐free environment, mimicking the development of young ovoviviparous fish inside their mothers' bodies in the absence of predators before birth.
The removal efficiency and mechanism of microplastic enhancement by positive modification dissolved air flotation
Authors: Wang Yonglei , Li Ya'nan , Tian Liping , Ju Ling , Liu Yulei
Published: May 2020

Microplastics (MPs) are widely distributed in freshwater and have the following characteristics: small size, strong hydrophobicity, difficult degradation, and easy adsorption of toxic substances. These characteristics pose a potential threat to the environment and human health. In this paper, three common MPs in freshwater were removed by conventional dissolved air flotation (DAF) and positive modification DAF (Posi‐DAF). The results showed that the optimal removal efficiency of MPs by conventional DAF was 32%–38% at 0.4–0.5 MPa. This indicated that the adhesion between microbubbles (MBs) and MPs was not ideal when the hydrophilic/hydrophobic interaction was the dominant mechanism. However, the removal efficiency of MPs was increased by 13.6%–33.7% compared with that of conventional DAF after two surface modifiers were used on MBs. This result indicated that in addition to the hydrophilic/hydrophobic interaction, both charge attraction and sweeping had positive effects.

Practitioner points

The removal efficiency and mechanism of MPs by posi‐DAF were investigated.

The characteristics, particle number, and adhesion of microplastics were measured.

Conventional DAF was dominated by hydrophilic/hydrophobic interactions.

CTAB Posi‐DAF was dominated by charge attraction.

PDADMAC Posi‐DAF was dominated by charge attraction and sweeping.
Infralimbic cortex activity is required for the expression but not the acquisition of conditioned safety
Authors: Kreutzmann Judith C. , Jovanovic Tanja , Fendt Markus
Published: May 2020

The ability to discriminate between danger and safety is crucial for survival across species. Whereas danger signals predict the onset of a potentially threatening event, safety signals indicate the non-occurrence of an aversive event, thereby reducing fear and stress responses. While the neural basis of conditioned safety remains to be elucidated, fear extinction studies provide evidence that the infralimbic cortex (IL) modulates fear inhibition. In the current study, the IL was temporarily inactivated with local muscimol injections in male and female rats. The effect of IL inactivation on the acquisition and expression of conditioned safety was investigated utilizing the startle response. Temporary inactivation of the IL prior to conditioning did not affect the acquisition of conditioned safety, whereas IL inactivation during the expression test completely blocked the expression of conditioned safety in male and female rats. Inactivation of the neighboring prelimbic (PL) cortex during the expression test did not affect the expression of safety memory. Our findings suggest that the IL is a critical brain region for the expression of safety memory. Because patients suffering from anxiety disorders are often unable to make use of safety cues to inhibit fear, the present findings are of clinical relevance and could potentially contribute to therapy optimization of anxiety-related psychiatric disorders.
Imaging mass spectrometry to visualise increased acetylcholine in lungs of asthma model mice
Authors: Matsuda Takeshi , Suzuki Yuzo , Fujisawa Tomoyuki , Suga Yasunori , Saito Nobuyuki , Suda Takafumi , Yao Ikuko
Published: May 2020

Acetylcholine (ACh) is a crucial neurotransmitter that is involved in airway constriction. In fact, excessive ACh binding to M3 muscarinic receptor leads to airflow obstruction via smooth muscle contraction. Previous studies have suggested cholinergic malfunction in the pathogenesis of asthma; however, the distribution and abundance of ACh in asthmatic lungs remain unclear because of the challenges of imaging ACh in lung tissue. In this study, we successfully detected and visualised ACh in mouse lung tissue by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Here, we applied the ACh imaging method to the two groups of house dust mite-sensitised asthma model mice harbouring different inflammatory levels. The imaging results showed that the lungs of mice had a relatively uniform ACh distribution with some areas of heterogeneity. The lungs of asthma model mice had significantly more ACh than control mice, and the ACh increase was potentiated with intense eosinophil infiltration without acetylcholinesterase deficits. These results indicate that ACh hypersecretion is mediated by an increased infiltration of eosinophils in asthma aggravation. This study provides the first evidence that secreted ACh is elevated with asthma severity in the lungs of asthma model animals by a direct ACh imaging technique with FT-ICR-MS.
How does extraction of biologically active substances with supercritical carbon dioxide affect lignocellulosic biomass properties?
Authors: Stolarski Mariusz Jerzy , Warmiński Kazimierz , Krzyżaniak Michał , Tyśkiewicz Katarzyna , Olba-Zięty Ewelina , Graban Łukasz , Lajszner Waldemar , Załuski Dariusz , Wiejak Rafał , Kamiński Piotr , Rój Edward
Published: May 2020

In the bio-based economy concept, any biomass should not be used directly for energy purposes without considering the possibility of using it for bioproducts with higher added value. Extractable phytochemicals found in lignocellulosic biomass of perennial industrial crops (PIC) are used in the pharmaceutical, cosmetics, chemical, food and feed industries. Therefore, these compounds should be obtained first, and only the so-called PIC extraction biomass should be used, for example, for the production of bioenergy. An efficient low-energy and environmentally friendly method of extracting phytochemicals from the plant biomass is supercritical carbon dioxide (scCO2) extraction. The aim of the study was to assess the thermophysical properties and chemical composition of 19 types of PIC biomass previously subjected to two types of scCO2extraction compared to the biomass before extraction. The biomass after pure scCO2and scCO2/H2O (1 wt%) extraction contained less ash (by 4.9 and 11.3%), carbon (by 3.1 and 7.8%), hydrogen (by 5.8 and 8.9%), nitrogen (by 4.5 and 6.8%), sulfur (by 3.8 and 3.8%), lignin (by 5.4 and 1.1%), hemicellulose (by 14.4%) and more chlorine (by 4.7 and 15.3%) compared to the biomass before extraction. In addition, the biomass after extraction with pure scCO2contained more cellulose and was characterized by lower moisture content and higher heating value and lower heating value. However, the biomass after scCO2/H2O extraction contained more substances soluble in cold and hot water. Generally, the bark of four short-rotation coppice (SRC) species was characterized by a high content of nitrogen, sulfur, substances soluble in cold and hot water, other soluble substances and at the same time low cellulose content (26–28% d.m.). In turn, the wood of all SRC species was characterized by a high cellulose content (51–56% d.m.). However, all herbaceous crops and grasses contained more chlorine, hemicellulose and generally less lignin compared to the SRC biomass. To assess the practical suitability of the PIC biomass extraction for the production of bioenergy (solid, liquid or gaseous biofuels), further research is needed.
The diagnostic role of diffusional kurtosis imaging in glioma grading and differentiation of gliomas from other intra-axial brain tumours: a systematic review with critical appraisal and meta-analysis
Authors: Abdalla Gehad , Dixon Luke , Sanverdi Eser , Machado Pedro M. , Kwong Joey S. W. , Panovska-Griffiths Jasmina , Rojas-Garcia Antonio , Yoneoka Daisuke , Veraart Jelle , Van Cauter Sofie , Abdel-Khalek Ahmed M. , Settein Magdy , Yousry Tarek , Bisdas Sotirios
Published: May 2020

Purpose

We aim to illustrate the diagnostic performance of diffusional kurtosis imaging (DKI) in the diagnosis of gliomas.

Methods

A review protocol was developed according to the (PRISMA-P) checklist, registered in the international prospective register of systematic reviews (PROSPERO) and published. A literature search in 4 databases was performed using the keywords ‘glioma’ and ‘diffusional kurtosis’. After applying a robust inclusion/exclusion criteria, included articles were independently evaluated according to the QUADAS-2 tool and data extraction was done. Reported sensitivities and specificities were used to construct 2 × 2 tables and paired forest plots using the Review Manager (RevMan®) software. A random-effect model was pursued using the hierarchical summary receiver operator characteristics.

Results

A total of 216 hits were retrieved. Considering duplicates and inclusion criteria, 23 articles were eligible for full-text reading. Ultimately, 19 studies were eligible for final inclusion. The quality assessment revealed 9 studies with low risk of bias in the 4 domains. Using a bivariate random-effect model for data synthesis, summary ROC curve showed a pooled area under the curve (AUC) of 0.92 and estimated sensitivity of 0.87 (95% CI 0.78–0.92) in high-/low-grade gliomas’ differentiation. A mean difference in mean kurtosis (MK) value between HGG and LGG of 0.22 (95% CI 0.25–0.19) was illustrated (p value = 0.0014) with moderate heterogeneity (I2 = 73.8%).

Conclusion

DKI shows good diagnostic accuracy in the differentiation of high- and low-grade gliomas further supporting its potential role in clinical practice. Further exploration of DKI in differentiating IDH status and in characterising non-glioma CNS tumours is however needed.
Reduction of severe intraventricular hemorrhage, a tertiary single-center experience: incidence trends, associated risk factors, and hospital policy
Authors: Alotaibi Wafa Sattam M. , Alsaif Nada S. , Ahmed Ibrahim A. , Mahmoud Aly Farouk , Ali Kamal , Hammad Abdullah , Aldibasi Omar S. , Alsaif Saif A.
Published: May 2020

Objectives

To determine the incidence, trends, maternal and neonatal risk factors of severe intraventricular hemorrhage (IVH) among infants born 24–32 weeks and/or < 1500 g, and to evaluate the impact of changing of hospital policies and unit clinical practice on the IVH incidence.

Study design

Retrospective chart review of preterm infants with a gestational age (GA) of 24–326 weeks and/or weight of < 1500 g born at King Abdulaziz Medical City–Riyadh (KAMC-R), Saudi Arabia, from 2016 to 2018. Multivariate logistic regression model was constructed to determine the probability of developing severe IVH and identify associations with maternal and neonatal risk factors.

Results

Among 640 infants, the overall incidence of severe IVH was 6.4% (41 infants), and its rate decreased significantly, from 9.4% in 2016 to 4.5% and 5% in 2017 and 2018 (p = 0.044). Multivariate analysis revealed that caesarian section delivery decreased the risk of severe IVH in GA group 24–27 weeks (p = 0.045). Furthermore use of inotropes (p = 0.0004) and surfactant (p = 0.0003) increased the risk of severe IVH. Despite increasing use of inotropes (p = 0.024), surfactant therapy (p = 0.034), and need for delivery room intubation (p = 0.015), there was a significant reduction in the incidence of severe IVH following the change in unit clinical practice and hospital policy (p = 0.007).

Conclusion

Cesarean section was associated with decreased all grades of IVH and severe IVH, while use of inotropes was associated with increased severe IVH. The changes in hospital and unit policy were correlated with decreased IVH during the study period.
COPD Assessment Test Changes from Baseline Correlate with COPD Exacerbations: A Longitudinal Analysis of the DACCORD Observational Study
Authors: Kardos Peter , Vogelmeier Claus F. , Worth Heinrich , Buhl Roland , Obermoser Victoria , Criée Carl-Peter
Published: May 2020

Purpose

A number of analyses have shown the immediate impact of COPD exacerbations on health status. However, none evaluated the long-term correlation between health status and the occurrence of exacerbations.

Methods

DACCORD is an observational study in patients with COPD recruited across Germany following initiation or change in COPD maintenance medication. Data collected include COPD Assessment Test (CAT) total score on entry and after 1 and 2 years, and the occurrence of exacerbations. We analysed the correlation between change from baseline in CAT total score and exacerbations, after excluding patients who exacerbated during the quarter immediately prior to the CAT assessment of interest.

Results

The initial correlation analysis was performed in 6075 patients, 28% with ≥ 1 exacerbation over the 2-year follow-up, and 58% with a clinically relevant CAT improvement. There was a significant correlation between exacerbations over 2 years and CAT change from baseline at Year 2 (p = 0.0041). The Spearman’s correlation coefficient was 0.03711, indicating very weak correlation—potentially driven by the high proportion of non-exacerbating patients. In a subsequent logistic regression, the probability of experiencing frequent (≥ 2 per year) or severe exacerbations was higher in patients with worsening in CAT total score (p < 0.001). However, the probability of a patient exacerbating in Year 1 or Year 2 did not correlate with CAT change.

Conclusions

In this population (initiating or changing maintenance COPD medication), patients with frequent or severe exacerbations had a long-term worsening in health status (beyond the acute effect of an exacerbation) compared with patients who do not exacerbate.
Exome sequencing in 38 patients with intracranial aneurysms and subarachnoid hemorrhage
Authors: Sauvigny Thomas , Alawi Malik , Krause Linda , Renner Sina , Spohn Michael , Busch Alice , Kolbe Verena , Altmüller Janine , Löscher Britt-Sabina , Franke Andre , Brockmann Christian , Lieb Wolfgang , Westphal Manfred , Schmidt Nils Ole , Regelsberger Jan , Rosenberger Georg
Published: May 2020

Objective

Genetic risk factors for unruptured intracranial aneurysms (UIA) and aneurysmal subarachnoid hemorrhage (aSAH) are poorly understood. We aimed to verify recently reported risk genes and to identify novel sequence variants involved in the etiology of UIA/aSAH.

Methods

We performed exome sequencing (ES) in 35 unrelated individuals and 3 family members, each with a history of UIA and/or aSAH. We searched for sequence variants with minor allele frequency (MAF) ≤ 5% in the reported risk genes ADAMTS15, ANGPTL6, ARHGEF17, LOXL2, PCNT, RNF213, THSD1 and TMEM132B. To identify novel putative risk genes we looked for unknown (MAF = 0) variants shared by the three relatives.

Results

We identified 20 variants with MAF ≤ 5% in 18 individuals: 9 variants in PCNT (9 patients), 4 in RNF213 (3 patients), 3 in THSD1 (6 patients), 2 in ANGPTL6 (3 patients), 1 in ADAMTS15 (1 patient) and 1 in TMEM132B (1 patient). In the affected family, prioritization of shared sequence variants yielded five novel putative risk genes. Based on predicted pathogenicity of identified variants, population genetics data and a high functional relevance for vascular biology, EDIL3 was selected as top candidate and screened in additional 37 individuals with UIA and/or aSAH: a further very rare EDIL3 sequence variant in two unrelated sporadic patients was identified.

Conclusions

Our data support a role of sequence variants in PCNT, RNF213 and THSD1 as susceptibility factors for cerebrovascular disease. The documented function in vascular wall integrity, the crucial localization of affected amino acids and gene/variant association tests suggest EDIL3 as a further valid candidate disease gene for UIA/aSAH.
Occupational differences in disability retirement due to a shoulder lesion: do work-related factors matter?
Authors: Sirén Maria , Viikari-Juntura Eira , Arokoski Jari , Solovieva Svetlana
Published: May 2020

Objective

To identify occupations with a high risk of disability retirement due to a shoulder lesion and to examine the effect of physical and psychosocial work-related factors on occupational differences in disability retirement.

Methods

We followed Finnish wage earners aged 30–59 years (n = 1,135,654) from 2005 to 2014 for full disability retirement due to a shoulder lesion. The work-related exposures were assessed with job exposure matrices. We calculated age-adjusted incidence rates and hazard ratios to test for the association between occupation and disability retirement due to a shoulder lesion. We also examined the contribution of work-related exposures to the excess risk of disability retirement.

Results

As compared to professionals, the age-adjusted risk of disability retirement was increased among men in all occupational groups except managers and customer service clerks and among women in several occupational groups. Adjustment for education attenuated the occupational differences considerably, particularly among women. The physical work-related factors fully explained the excess risk of disability retirement due to a shoulder lesion among male finance and sales associate professionals and administrative secretaries as well as among agricultural and fishery workers. In women, the physical work-related factors fully explained the excess risk among construction workers, electricians and plumbers. For both genders, the contribution of psychosocial factors to excess risk of disability retirement was modest and seen for monotonous work only.

Conclusions

A reduction of the level of physical work load factors as well as monotonousness of work has a potential to prevent work disability due to a shoulder lesion.
Influencing factors of cardiorespiratory fitness in allogeneic stem cell transplant candidates prior to transplantation
Authors: Limbach Matthias , Kuehl Rea , Dreger Peter , Luft Thomas , Rosenberger Friederike , Kleindienst Nikolaus , Friedmann-Bette Birgit , Bondong Andrea , Bohus Martin , Wiskemann Joachim
Published: May 2020

Purpose

Cardiorespiratory fitness (CRF) seems to be prognostic prior to allogeneic stem cell transplantation (allo-HSCT). Influencing factors of CRF in allo-HSCT candidates have not been studied so far. Aim was to identify potentially influencing factors on CRF.

Methods

To assess CRF, a maximal cardiopulmonary exercise test (CPET) was performed on average 2.6 ± 7.2 days prior to admission. A regression analysis was conducted, with the following predictors: gender, age, body mass index (BMI), time between last therapy and allo-HSCT (t_Therapies), number of cardiotoxic therapies (n_Cardiotox), number of transplantations (n_Transplantations), comorbidity index (HCT-CI), hemoglobin level of the last 3 months (area under the curve), and physical activity.

Results

A total of 194 patients performed a CPET. VO2peak was significantly reduced compared with reference data. In total, VO2peak was 21.4 ml/min/kg (− 27.5%, p < 0.05). Men showed a significant larger percentage difference from reference value (− 29.1%, p < 0.05) than women (− 24.4%). VO2peak was significantly (p < 0.05) influenced by age (β = − 0.11), female gender (β = − 3.01), BMI (β = − 0.44), n_Cardiotox (β = − 0.73), hemoglobin level (β = 0.56), and physical activity prior to diagnosis (β = 0.10).

Conclusions

Our study demonstrates a decreased CRF indicating the potential need of prehabilitative exercise. We revealed some influencing factors on CRF. Those patients could benefit the most from exercise.
The links between the Madden-Julian Oscillation and European weather regimes
Authors: Lee Joshua Chun Kwang , Lee Robert William , Woolnough Steven James , Boxall Luke John
Published: May 2020

Skillful weather forecasting on sub-seasonal timescales is important to enable users to make cost-effective decisions. Forecast skill can be expected to be mediated by the prediction of atmospheric flow patterns, often known as weather regimes, over the relevant region. Here, we show how the Grosswetterlagen (GWL), a set of 29 European weather regimes, can be modulated by the extra-tropical teleconnection from the Madden-Julian Oscillation (MJO). Together, these GWL regimes represent the large-scale flow characteristics observed in the four North Atlantic-European classical weather regimes (NAE-CWRs), while individually capturing synoptic scale flow details. By matching each GWL regime to the nearest NAE-CWR, we reveal GWL regimes which occur during the transition stages between the NAE-CWRs and show the importance of capturing the added synoptic detail of GWL regimes when determining their teleconnection pattern from the MJO. The occurrence probabilities of certain GWL regimes are significantly changed 10–15 days after certain MJO phases, exhibiting teleconnection patterns similar to their NAE-CWR matches but often with larger occurrence anomalies, over fewer consecutive MJO phases. These changes in occurrence probabilities are likely related to MJO-induced changes in the persistence and transition probabilities. Other GWL regimes are not significantly influenced by the MJO. These findings demonstrate how the MJO can modify the preferred evolution of the NAE atmospheric flow, which is important for sub-seasonal weather forecasting.
Hydrogeological characterization of an alpine aquifer system in the Canadian Rocky Mountains
Authors: Christensen Craig William , Hayashi Masaki , Bentley Laurence R.
Published: May 2020

Groundwater storage in alpine regions is essential for maintaining baseflows in mountain streams. Recent studies have shown that common alpine landforms (e.g., talus and moraine) have substantial groundwater storage capacity, but the hydrogeological connectivity between individual landforms has not been understood. This study characterizes the hydrogeology of an alpine cirque basin in the Canadian Rocky Mountains that contains typical alpine landforms (talus, meadow, moraines) and hydrological features (tarn, streams, and springs). Geological, hydrological, and hydrochemical observations were used to understand the overall hydrogeological setting of the study basin, and three different geophysical methods (electrical resistivity tomography, seismic refraction tomography, and ground penetrating radar) were used to characterize the subsurface structure and connectivity, and to develop a hydrogeological conceptual model. Geophysical imaging shows that the talus is typically 20–40 m thick and highly heterogeneous. The meadow sediments are only up to 11 m thick but are part of a 30–40-m-thick accumulation of unconsolidated material that fills a bedrock overdeepening (i.e. a closed, subglacial basin). A minor, shallow groundwater system feeds springs on the talus and streams on the meadow, whereas a deep system in the moraine supplies most of the water to the basin outlet springs, thereby serving as a ‘gate keeper’ of the basin. Although the hydrologic functions of the talus in this study are substantially different from other locations, primarily due to differences in bedrock lithology and geomorphic processes, the general conceptual framework developed in this study is expected to be applicable to other alpine regions.
Fine-tuning the regulation of Cas9 expression levels for efficient CRISPR-Cas9 mediated recombination in Streptomyces
Authors: Ye Suhui , Enghiad Behnam , Zhao Huimin , Takano Eriko
Published: May 2020

CRISPR-Cas9 has proven as a very powerful gene editing tool for Actinomyces, allowing scarless and precise genome editing in selected strains of these biotechnologically relevant microorganisms. However, its general application in actinomycetes has been limited due to its inefficacy when applying the system in an untested strain. Here, we provide evidence of how Cas9 levels are toxic for the model actinomycetes Streptomyces coelicolor M145 and Streptomyces lividans TK24, which show delayed or absence of growth. We overcame this toxicity by lowering Cas9 levels and have generated a set of plasmids in which Cas9 expression is either controlled by theophylline-inducible or constitutive promoters. We validated the targeting of these CRISPR-Cas9 system using the glycerol uptake operon and the actinorhodin biosynthesis gene cluster. Our results highlight the importance of adjusting Cas9 expression levels specifically in strains to gain optimum and efficient gene editing in Actinomyces.
Psychological resilience and active aging among older people with mobility limitations
Authors: Siltanen Sini , Tourunen Anu , Saajanaho Milla , Palmberg Lotta , Portegijs Erja , Rantanen Taina
Published: May 2020

Active aging refers to striving for well-being through preferred activity and may be restricted with declining mobility. We investigated whether psychological resilience, i.e., the ability to tolerate hardship, can aid older people in being active despite mobility limitations. Participants were 961 community-dwelling persons aged 75, 80, or 85 years living in Jyväskylä, Central Finland. Mobility limitations were indicated as self-reported difficulty in walking 2 km. Categories were no difficulty (reference), difficulty, and unable to walk. Resilience was assessed with the 10-item Connor–Davidson Resilience Scale and active aging with the University of Jyvaskyla Active Aging scale. Data were analyzed with OLS regression analyses, which were stratified by age. In all age-groups, having difficulties walking or being unable to walk 2 km was associated with lower active aging scores. Resilience moderated this association especially among the 75-year-olds, but not among the 85-year-olds: The higher the resilience score, the higher the active aging score among those reporting no or some walking difficulties. Those unable to walk 2 km had lower active aging scores irrespective of resilience level. Psychological resilience may alleviate the negative effects of early phase walking difficulties on active aging but may be insufficient to compensate for more severe walking limitations that restrict not only function but also autonomy.
Synthesis of the Thomsen-Friedenreich-antigen (TF-antigen) and binding of Galectin-3 to TF-antigen presenting neo-glycoproteins
Authors: Hoffmann Marius , Hayes Marc R. , Pietruszka Jörg , Elling Lothar
Published: May 2020

The Thomsen-Friedenreich-antigen, Gal(β1–3)GalNAc(α1-O-Ser/Thr (TF-antigen), is presented on the surface of most human cancer cell types. Its interaction with galectin 1 and galectin 3 leads to tumor cell aggregation and promotes cancer metastasis and T-cell apoptosis in epithelial tissue. To further explore multivalent binding between the TF-antigen and galectin-3, the TF-antigen was enzymatically synthesized in high yields with GalNAc(α1-EG3-azide as the acceptor substrate by use of the glycosynthase BgaC/Glu233Gly. Subsequently, it was coupled to alkynyl-functionalized bovine serum albumin via a copper(I)-catalyzed alkyne-azide cycloaddition. This procedure yielded neo-glycoproteins with tunable glycan multivalency for binding studies. Glycan densities between 2 and 53 glycan residues per protein molecule were obtained by regulated alkynyl-modification of the lysine residues of BSA. The number of coupled glycans was quantified by sodium dodecyl sulfate polyacrylamide gel electrophoresis and a trinitrobenzene sulfonic acid assay. The binding efficiency of the neo-glycoproteins with human galectin-3 and the effect of multivalency was investigated and assessed using an enzyme-linked lectin assay. Immobilized neo-glycoproteins of all modification densities showed binding of Gal-3 with increasing glycan density. However, multivalent glycan presentation did not result in a higher binding affinity. In contrast, inhibition of Gal-3 binding to asialofetuin was effective. The relative inhibitory potency was increased by a factor of 142 for neo-glycoproteins displaying 10 glycans/protein in contrast to highly decorated inhibitors with only 2-fold increase. In summary, the functionality of BSA-based neo-glycoproteins presenting the TF-antigen as multivalent inhibitors for Gal-3 was demonstrated.
Erfolg und Misserfolg von kommunikationswissenschaftlichen DFG-Forschungsverbünden: Bilanz, Faktoren, Konsequenzen
Authors: Vowe Gerhard , Meißner Florian
Published: May 2020

Wie können die Chancen des Erfolgs von Anträgen bei der DFG auf Finanzierung kommunikationswissenschaftlicher Forschungsverbünde erhöht werden? Der Beitrag gibt eine Antwort in drei Schritten.

(1) Bilanz: In den letzten zehn Jahren wurden mindestens 38 Anträge auf Forschungsverbünde mit kommunikationswissenschaftlicher Beteiligung gestellt; davon war ca. die Hälfte erfolgreich. Um 2010 starteten drei mittelgroße Verbünde und danach noch einige kleine internationale Verbünde. Die Aktivitäten in der Verbundforschung haben sich zwar deutlich intensiviert, aber die Kommunikationswissenschaft schöpft ihr gewachsenes Potenzial bei weitem nicht aus. Sie liegt bei Forschungsverbünden, aber auch bei Einzelprojekten pro Professur, weit hinter den anderen Sozialwissenschaften zurück und erst recht hinter Fächern aus anderen Wissenschaftsbereichen. Diese Kluft hat sich mit dem Ausbau der Kommunikationswissenschaft sogar noch vergrößert.

(2) Diagnose: Über Erfolg und Misserfolg von Anträgen entscheiden sechs Faktoren, und zwar Antragsqualität, Qualifikationsprofil der Antragstellenden, Kompetenz der Gutachtenden, Entscheidungsprozesse in Gremien, Unterstützung durch Universitätsleitungen und Inanspruchnahme der DFG-Beratung.

(3) Konsequenzen: Um die Wahrscheinlichkeit von Erfolgen zu erhöhen, sollten die fünf zentralen Akteure vor allem Folgendes tun:

Potenzielle Initiatorinnen und Initiatoren sollten DFG-Forschungsverbünden höhere Priorität einräumen als bisher und als anderen Aufgaben.

Gutachtende sollten konsistent argumentieren, also begründet befürworten oder ablehnen, aber eine Befürwortung nicht mit eigenen Vorschlägen verknüpfen.

Die DFG-Geschäftsstelle sollte fächerscharfe Daten zur Förderung verfügbar machen, um den Fächern zu ermöglichen, ihre Stärken und Schwächen zu erkennen.

Die Universitätsleitungen sollten die Beantragung von Forschungsverbünden stärker fördern und fordern.

Die DGPuK sollte dem Thema Forschungsverbünde höhere Priorität einräumen als bisher und zum Ziel setzen, dass zu den anderen Sozialwissenschaften aufgeschlossen wird.
Crystallization of Mechanically Alloyed Ni50Ti50 and Ti50Ni25Cu25 Shape Memory Alloys
Authors: Salwa Piotr , Goryczka Tomasz
Published: May 2020

The Ni50Ti50and Ti50Ni25Cu25alloys were produced in the form of powder using the high-energy ball milling. In the as-milled state, both alloys revealed presence of an amorphous state with a small amount of nanocrystalline areas. The non-isothermal DSC heating curves were used to investigate the crystallization process. Temperatures and activation energy of crystallization were determined. In both alloys, the crystallization occurred at temperatures range from 777 to 813 K, dependently on the heating rate. The activation energy values determined by the Kissinger and Ozawa method were comparable for both alloys and ranged from 410 to 429 kJ/mol.
Transgenic Overexpression of the Disordered Prion Protein N1 Fragment in Mice Does Not Protect Against Neurodegenerative Diseases Due to Impaired ER Translocation
Authors: Mohammadi Behnam , Linsenmeier Luise , Shafiq Mohsin , Puig Berta , Galliciotti Giovanna , Giudici Camilla , Willem Michael , Eden Thomas , Koch-Nolte Friedrich , Lin Yu-Hsuan , Tatzelt Jörg , Glatzel Markus , Altmeppen Hermann C.
Published: May 2020

The structurally disordered N-terminal half of the prion protein (PrPC) is constitutively released into the extracellular space by an endogenous proteolytic cleavage event. Once liberated, this N1 fragment acts neuroprotective in ischemic conditions and interferes with toxic peptides associated with neurodegenerative diseases, such as amyloid-beta (Aβ) in Alzheimer’s disease. Since analog protective effects of N1 in prion diseases, such as Creutzfeldt-Jakob disease, have not been studied, and given that the protease releasing N1 has not been identified to date, we have generated and characterized transgenic mice overexpressing N1 (TgN1). Upon intracerebral inoculation of TgN1 mice with prions, no protective effects were observed at the levels of survival, clinical course, neuropathological, or molecular assessment. Likewise, primary neurons of these mice did not show protection against Aβ toxicity. Our biochemical and morphological analyses revealed that this lack of protective effects is seemingly due to an impaired ER translocation of the disordered N1 resulting in its cytosolic retention with an uncleaved signal peptide. Thus, TgN1 mice represent the first animal model to prove the inefficient ER translocation of intrinsically disordered domains (IDD). In contrast to earlier studies, our data challenge roles of cytoplasmic N1 as a cell penetrating peptide or as a potent “anti-prion” agent. Lastly, our study highlights both the importance of structured domains in the nascent chain for proteins to be translocated and aspects to be considered when devising novel N1-based therapeutic approaches against neurodegenerative diseases.
A Prospective Pilot Study to Identify a Myocarditis Cohort who may Safely Resume Sports Activities 3 Months after Diagnosis
Authors: Patriki D. , Baltensperger N. , Berg J. , Cooper L. T. , Kissel C. K. , Kottwitz J. , Lovrinovic M. , Manka R. , Scherff F. , Schmied C. , Tanner F. C. , Luescher T. F. , Heidecker Bettina
Published: May 2020

International cardiovascular society recommendations to return to sports activities following acute myocarditis are based on expert consensus in the absence of prospective studies. We prospectively enrolled 30 patients with newly diagnosed myocarditis based on clinical parameters, laboratory measurements and cardiac magnetic resonance imaging with mildly reduced or preserved left ventricular ejection fraction (LVEF) with a follow-up of 12 months. Cessation of physical activity was recommended for 3 months. The average age was 35 (19–80) years with 73% male patients. One case of non-sustained ventricular tachycardia was recorded during 48-h-Holter electrocardiogram. Except for this case, all patients were allowed to resume physical exercise after 3 months. At 6- (n = 26) and 12-month (n = 19) follow-up neither cardiac events nor worsening LVEF were recorded. The risk of cardiac events at 1 year after diagnosis of myocarditis appears to be low after resumption of exercise after 3 months among patients who recover from acute myocarditis.
The Assessment of the Paediatric Athlete
Authors: Pieles Guido E. , Oberhoffer Renate
Published: May 2020

The success of systematic early age talent development has led to the professionalisation of youth sports academies used by clubs and governing bodies alike, and sports physicians are nowadays commonly confronted with paediatric cardiological problems. Medical cardiac care of the paediatric athlete is however in its infancy, and the international guidelines that are present for adult athletes, are not yet available. Similarly, reference data for ECG and echocardiography are incomplete. The aim of this article is to provide and introduction to the cardiac care of the paediatric athlete to facilitate healthy and above all, safe talent development, but also provide guidance on how to distinguish adaptive, beneficial cardiovascular remodelling from underlying pathology of congenital or inherited cardiovascular disease. Differences in presentation, diagnosis and treatment between childhood and adult athletes are highlighted and can educate the reader in the emerging field of paediatric sports cardiology.