julilili42/papers huggingface dataset:
Xenopus oocytes as a heterologous expression system for analysis of tight junction proteins
2019-01-15

ABSTRACT Claudins (cldns) represent the largest family of transmembrane tight junction (TJ) proteins, determining organ‐specific epithelial barrier properties. Because methods for the analysis of multiple cldn interaction are limited, we have established the heterologous Xenopus laevis oocyte expression system for TJ protein assembly and interaction analysis. Oocytes were injected with cRNA encoding human cldn‐1, ‐2, or ‐3 or with a combination of these and were incubated in pairs for interaction analysis. Immunoblotting and immunohistochemistry were performed, and membrane contact areas were analyzed morphometrically and by freeze fracture electron microscopy. Cldns were specifically detected in membranes of expressing oocytes, and coincubation of oocytes resulted in adhesive contact areas that increased with incubation time. Adjacent membrane areas revealed specific cldn signals, including “kissing‐point”–like structures representing homophilic trans ‐interactions of cldns. Contact areas of oocytes expressing a combination markedly exceeded those expressing single cldns, indicating effects on adhesion. Ultra‐structural analysis revealed a self‐assembly of TJ strands and a cldn‐specific strand morphology.—Vitzthum, C., Stein, L., Brunner, N., Knittel, R., Fallier‐Becker, P., Amasheh, S. Xenopus oocytes as a heterologous expression system for analysis of tight junction proteins. FASEB J. 33, 5312–5319 (2019). www.fasebj.org
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastases in Solid Organ Graft Recipients: First Experience
2019-01-15

BACKGROUND Therapy of peritoneal metastases (PM) in solid organ transplant recipients is challenging. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might constitute a new therapeutic opportunity for these patients. MATERIAL AND METHODS This was a single-center, retrospective analysis of prospective registry data (NCT03210298) in a tertiary care center between 1.7.2016 and 31.12.2017. Intraperitoneal administration of oxaliplatin 92 mg/m2 body surface or a combination of cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2, repeated every 6 weeks. Objective tumor response was documented via histology (Peritoneal Regression Grading Score, PRGS), adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) 4.0. RESULTS Out of 71 consecutive patients treated with PIPAC, 2 patients (2.8%) were solid organ transplant recipients. The first patient had metachronous PM of colonic cancer origin after liver transplantation. The second patient had synchronous PM of pancreatic cancer origin after combined kidney-pancreas transplantation. After repeated combined systemic and PIPAC chemotherapy, objective histological response was documented in both patients. No adverse events >CTCAE 2 were recorded. There was no measurable liver or renal toxicity. PIPAC procedures could be repeated (2, resp. 3 cycles) without any interruption of immunosuppressive medication or impairment of respective plasmatic drug levels. The first patient passed away 7 months after the first PIPAC, the second patient was still alive after 8 months. CONCLUSIONS PIPAC can induce objective regression of PM in solid organ transplant recipients without inducing organ toxicity or interfering with immunosuppressive therapy.
Desmoplastic small round cell tumors: Multimodality treatment and new risk factors
2019-01-16

Abstract Background To evaluate optimal therapy and potential risk factors. Methods Data of DSRCT patients &lt;40 years treated in prospective CWS trials 1997‐2015 were analyzed. Results Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high‐dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three‐year event‐free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra‐abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse. Conclusion Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.
The Relationship Between Networking,LinkedInUse, and Retrieving Informational Benefits
2019-01-16

Previous research has shown that users of social network sites designed for professional purposes, such as LinkedIn, report higher professional informational benefits than nonusers. However, this effect could only be partly explained by social media use as there was also a selection effect, such that people who have more informational benefits were more likely to use LinkedIn. The goal of this study was to explore whether differences in networking, defined as a set of behaviors with the aim of building, maintaining, and using internal and external contacts for instrumental purposes, can explain this selection effect. We used data from a panel study with a representative sample of Dutch Internet users (n = 685; 259 LinkedIn users) to examine the relationships between networking and LinkedIn use as well as professional informational benefits, that is, timely access to relevant information. The results showed that people scoring high on external networking (but not internal networking within their organization) are also more likely to use LinkedIn. External networking was also positively correlated with active and passive use as well as the number of strong and latent ties on LinkedIn. However, in a mediation model the direct effect of networking on informational benefits was not mediated by actual social media use and network composition; instead, the number of weak ties had a direct effect on informational benefits. The results thus indicate that networking is a major driver of informational benefits from LinkedIn use.
Hydration of calcium aluminates at 60°C – Development paths of C 2 AH x in dependence on the content of free water
2019-01-16

Abstract The influence of water loss during the hydration of calcium aluminates on the phase development is investigated at 60°C. This is relevant for applications in which calcium aluminate cement ( CAC ) based formulations are exposed to quick drying during hydration. The presented results provide new insights into the well‐known conversion processes occurring in CAC pastes. Using in situ XRD two different routes of the development of initially formed C 2 AH 8 are determined: (a) transformation to C 3 AH 6 + AH 3 in the presence of sufficient free water and (b) dehydration to C 2 AH 5 at a lack of free water. Moreover, the influence of precuring of the pastes at 23°C before heating to 60°C is investigated. The increasing loss of free water with increasing precuring time resulting from both, precipitation of hydrate phases and evaporation, causes incomplete hydration of CA or CA 2 as well as dehydration of C 2 AH 8 instead of conversion into C 3 AH 6 . Comparative investigations of sealed samples always revealed complete hydration of CA and CA 2 as well as complete conversion of C 2 AH 8 .
Epigenetic Modifications of the Liver Tumor Cell Line HepG2 Increase Their Drug Metabolic Capacity
2019-01-16

Although human liver tumor cells have reduced metabolic functions as compared to primary human hepatocytes (PHH) they are widely used for pre-screening tests of drug metabolism and toxicity. The aim of the present study was to modify liver cancer cell lines in order to improve their drug-metabolizing activities towards PHH. It is well-known that epigenetics is strongly modified in tumor cells and that epigenetic regulators influence the expression and function of Cytochrome P450 (CYP) enzymes through altering crucial transcription factors responsible for drug-metabolizing enzymes. Therefore, we screened the epigenetic status of four different liver cancer cell lines (Huh7, HLE, HepG2 and AKN-1) which were reported to have metabolizing drug activities. Our results showed that HepG2 cells demonstrated the highest similarity compared to PHH. Thus, we modified the epigenetic status of HepG2 cells towards ‘normal’ liver cells by 5-Azacytidine (5-AZA) and Vitamin C exposure. Then, mRNA expression of Epithelial-mesenchymal transition (EMT) marker SNAIL and CYP enzymes were measured by PCR and determinate specific drug metabolites, associated with CYP enzymes by LC/MS. Our results demonstrated an epigenetic shift in HepG2 cells towards PHH after exposure to 5-AZA and Vitamin C which resulted in a higher expression and activity of specific drug metabolizing CYP enzymes. Finally, we observed that 5-AZA and Vitamin C led to an increased expression of Hepatocyte nuclear factor 4α (HNF4α) and E-Cadherin and a significant down regulation of Snail1 (SNAIL), the key transcriptional repressor of E-Cadherin. Our study shows, that certain phase I genes and their enzyme activities are increased by epigenetic modification in HepG2 cells with a concomitant reduction of EMT marker gene SNAIL. The enhancing of liver specific functions in hepatoma cells using epigenetic modifiers opens new opportunities for the usage of cell lines as a potential liver in vitro model for drug testing and development.
Asymmetry of an epicontinental basin—facies, cycles, tectonics and hydrodynamics: The Triassic Upper Muschelkalk, South Germanic Basin
2019-01-16

Abstract The Middle Triassic–Upper Muschelkalk deposits of central Europe form an excellent, “laboratory‐scale” outcrop analogue for subsurface hydrocarbon reservoirs in epeiric basins. This study provides a detailed sedimentological analysis at microfacies to basin‐wide scales within a well‐constrained biostratigraphic and sequence stratigraphic framework. The database comprises 31 outcrops and 27 drill cores in the southern part of the Triassic Germanic Basin, from Luxembourg, eastern France, northern Switzerland and southwestern Germany. The Upper Muschelkalk comprises 21 lithofacies types which are grouped into eight distinct lithofacies associations encompassing coastal sabkha, peritidal, backshoal, shoal, shoal fringe, foreshoal to offshoal environments. A 1D sequence stratigraphic framework was established on different cyclic scales ranging from depositional sequences, cycle sets, cycles to mini‐cycles. Regional 2D correlations based on 1D cycle analysis and biostratigraphic conodont/ceratite zonation reveal the temporal and spatial distribution of reservoir bodies and the morphological variance of 1D cycles across the carbonate ramp. A basin‐wide W–E ‘coast to coast’ cross‐section shows an asymmetric basin architecture with significant differences in facies distribution, cycle morphology, and consequently sizes of potential reservoir bodies. This distinct asymmetry is controlled by the palaeo‐tectonic setting (quiet versus more active) and the hydrodynamics (windward versus leeward, inflow of freshwater versus marine waters) which differs from coast to coast. Such asymmetric patterns will have to be considered in exploration scenarios of subsurface hydrocarbon‐bearing epeiric basins in the Middle East and elsewhere.
Modulations of event-related potentials by tactile negative priming
2019-01-16

Negative priming (NP) refers to the finding that responses to previously irrelevant stimuli are impeded relative to responses to new stimuli. To date, NP has been demonstrated in the visual, auditory, and tactile sensory modalities with both inhibitory processes and retrieval-based processes contributing to the effect. To gain deeper insights into the role of both processes, event-related potentials (ERPs) have been measured during NP tasks with visual and separately with auditory stimuli. The specific patterns of ERP correlates are mixed, yet it can generally be concluded from previous research that amplitudes of both the N2 and the P3 reflect important components of NP. We present the first study to assess the ERP correlates of NP in the tactile modality. We observe a significant modulation of the P3 but not of the N2, thus providing tentative support for the existence of modality-specific differences in the ERP correlates of NP.
Eckhart, Heidegger and Caputo: a reappraisal of ‘the mystical element in Heidegger’s thought’
2019-01-16

This article aims at a reconsideration and a reappraisal of the mystical nature of Martin Heidegger’s thought in juxtaposition with the mystical theology of Meister Eckhart. My purpose here is to demonstrate the similarities between the thoughts of the two authors and to maintain the relevancy of Heidegger’s works to our contemporary times. It is my own conviction that contemporary theology must move beyond the pure metaphysical and scientific ways of doing theology towards a more open, spiritual and mystical perception of the divine, and that Heidegger’s works can be used as tool for making this move. Thus, contrary to John D. Caputo, who claimed that the similarity between the two thinkers – Eckhart and Heidegger – is a similarity of structure, rather than content, and that Eckhart failed in destroying metaphysics while Heidegger’s thought is ‘dangerous’ and ‘ominous’, I argue here further that the similarity between the two is similarity of content, and that the works of the two authors have a perpetual value, within the fields of both philosophy and theology.
Report on 1811.05728v2
2019-01-16

We use machine learning methods to approximate a classical density functional.The functional 'learns' by comparing the density profile it generates with that of simulations.As a study case, we choose the model problem of a Lennard-Jones fluid in one dimension where there is no exact solution available.After separating the excess free energy functional into a "repulsive" and an "attractive" part, machine learning finds a functional for the attractive part in weighted-density form.The predictions of density profile at a hard wall shows good agreement when subject to thermodynamic conditions beyond those in the training set.This also holds for the equation of state if this is evaluated near the training temperature.We discuss the applicability to problems in higher dimensions.
Short-Chain Fatty Acid Propionate Protects From Hypertensive Cardiovascular Damage
2019-01-17

Background: Arterial hypertension and its organ sequelae show characteristics of T cell–mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage. Methods: To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout–deficient mice received propionate (200 mmol/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg –1 ·d –1 subcutaneous) for 14 days. To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg·kg –1 ·d –1 subcutaneous) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate. Results: Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II–infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout–deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell–depleted angiotensin II–infused mice, suggesting the effect is regulatory T cell–dependent. Conclusions: Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease.
Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy
2019-01-17

Background: Acute stress-induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable with that of myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. Methods: In a multicenter study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age-, sex-, and comorbidity-matched control subjects. During the index event and at the 5-month follow-up, patients with takotsubo cardiomyopathy underwent multiparametric cardiac magnetic resonance imaging, including ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement for detection of inflammatory macrophages in the myocardium. Blood monocyte subpopulations and serum cytokines were assessed as measures of systemic inflammation. Matched control subjects underwent investigation at a single time point. Results: Subjects were predominantly middle-aged (64±14 years) women (90%). Compared with control subjects, patients with takotsubo cardiomyopathy had greater USPIO enhancement (expressed as the difference between pre-USPIO and post-USPIO T2*) in both ballooning (14.3±0.6 milliseconds versus 10.5±0.9 milliseconds; P &lt;0.001) and nonballooning (12.9±0.6 milliseconds versus 10.5±0.9 milliseconds; P =0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 pg/mL versus 6.5±5.8 pg/mL; P &lt;0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 pg/mL versus 1272±177 pg/mL; P =0.01) concentrations and classic CD14 ++ CD16 - monocytes (90±0.5% versus 87±0.9%; P =0.01) were also increased whereas intermediate CD14 ++ CD16 + (5.4±0.3% versus 6.9±0.6%; P =0.01) and nonclassic CD14 + CD16 ++ (2.7±0.3% versus 4.2±0.5%; P =0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium, although persistent elevations in serum interleukin-6 concentrations ( P =0.009) and reductions in intermediate CD14 ++ CD16 + monocytes (5.6±0.4% versus 6.9±0.6%; P =0.01) remained. Conclusions: We demonstrate for the first time that takotsubo cardiomyopathy is characterized by a myocardial macrophage inflammatory infiltrate, changes in the distribution of monocyte subsets, and an increase in systemic proinflammatory cytokines. Many of these changes persisted for at least 5 months, suggesting a low-grade chronic inflammatory state. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02897739.
Cancer-Associated Intermediate Conductance Ca2+-Activated K+ Channel KCa3.1
2019-01-17

Several tumor entities have been reported to overexpress KCa3.1 potassium channels due to epigenetic, transcriptional, or post-translational modifications. By modulating membrane potential, cell volume, or Ca2+ signaling, KCa3.1 has been proposed to exert pivotal oncogenic functions in tumorigenesis, malignant progression, metastasis, and therapy resistance. Moreover, KCa3.1 is expressed by tumor-promoting stroma cells such as fibroblasts and the tumor vasculature suggesting a role of KCa3.1 in the adaptation of the tumor microenvironment. Combined, this features KCa3.1 as a candidate target for innovative anti-cancer therapy. However, immune cells also express KCa3.1 thereby contributing to T cell activation. Thus, any strategy targeting KCa3.1 in anti-cancer therapy may also modulate anti-tumor immune activity and/or immunosuppression. The present review article highlights the potential of KCa3.1 as an anti-tumor target providing an overview of the current knowledge on its function in tumor pathogenesis with emphasis on vasculo- and angiogenesis as well as anti-cancer immune responses.
Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
2019-01-17

While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD.