julilili42/papers huggingface dataset:
Molecular Mechanisms of Induction of Tolerant and Tolerogenic Intestinal Dendritic Cells in Mice
2016-01-01

How does the host manage to tolerate its own intestinal microbiota? A simple question leading to complicated answers. In order to maintain balanced immune responses in the intestine, the host immune system must tolerate commensal bacteria in the gut while it has to simultaneously keep the ability to fight pathogens and to clear infections. If this tender equilibrium is disturbed, severe chronic inflammatory reactions can result. Tolerogenic intestinal dendritic cells fulfil a crucial role in balancing immune responses and therefore creating homeostatic conditions and preventing from uncontrolled inflammation. Although several dendritic cell subsets have already been characterized to play a pivotal role in this process, less is known about definite molecular mechanisms of how intestinal dendritic cells are converted into tolerogenic ones. Here we review how gut commensal bacteria interact with intestinal dendritic cells and why this bacteria-host cell interaction is crucial for induction of dendritic cell tolerance in the intestine. Hereby, different commensal bacteria can have distinct effects on the phenotype of intestinal dendritic cells and these effects are mainly mediated by impacting toll-like receptor signalling in dendritic cells.
Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells
2016-01-01

Disturbances in neuronal differentiation and function are an underlying factor of many brain disorders. Zinc homeostasis and signaling are important mediators for a normal brain development and function, given that zinc deficiency was shown to result in cognitive and emotional deficits in animal models that might be associated with neurodevelopmental disorders. One underlying mechanism of the observed detrimental effects of zinc deficiency on the brain might be impaired proliferation and differentiation of stem cells participating in neurogenesis. Thus, to examine the molecular mechanisms regulating zinc metabolism and signaling in differentiating neurons, using a protocol for motor neuron differentiation, we characterized the expression of zinc homeostasis genes during neurogenesis using human induced pluripotent stem cells (hiPSCs) and evaluated the influence of altered zinc levels on the expression of zinc homeostasis genes, cell survival, cell fate, and neuronal function. Our results show that zinc transporters are highly regulated genes during neuronal differentiation and that low zinc levels are associated with decreased cell survival, altered neuronal differentiation, and, in particular, synaptic function. We conclude that zinc deficiency in a critical time window during brain development might influence brain function by modulating neuronal differentiation.
Surgical Treatment of Early-Stage Cervical Cancer
2016-01-01

Surgical treatment of cervical cancer has been a cornerstone in the management of this malignancy for more than 100 years. Today, for early-stage and low-risk cervical cancer, surgery is still considered the gold standard. If the preoperative assessment of the tumor reveals a situation prompting postoperative adjuvant radiochemotherapy, the latter should be planned as the primary treatment option, being preceded by staging laparoscopy including pelvic and paraaortic lymph node dissection. As an alternative to the open approach, the definitive surgical treatment should be either performed laparoscopically, or be laparoscopic-assisted, or laparoscopically robotic-assisted.
Antisense Oligonucleotide Mediated Splice Correction of a Deep Intronic Mutation in OPA1
2016-01-01

Inherited optic neuropathies (ION) present an important cause of blindness in the European working-age population. Recently we reported the discovery of four independent families with deep intronic mutations in the main inherited optic neuropathies gene OPA1. These deep intronic mutations cause mis-splicing of the OPA1 pre-messenger-RNA transcripts by creating cryptic acceptor splice sites. As a rescue strategy we sought to prevent mis-splicing of the mutant pre-messenger-RNA by applying 2'O-methyl-antisense oligonucleotides (AONs) with a full-length phosphorothioate backbone that target the cryptic acceptor splice sites and the predicted novel branch point created by the deep intronic mutations, respectively. Transfection of patient-derived primary fibroblasts with these AONs induced correct splicing of the mutant pre-messenger-RNA in a time and concentration dependent mode of action, as detected by pyrosequencing of informative heterozygous variants. The treatment showed strong rescue effects (~55%) using the cryptic acceptor splice sites targeting AON and moderate rescue (~16%) using the branch point targeting AON. The highest efficacy of Splice correction could be observed 4 days after treatment however, significant effects were still seen 14 days post-transfection. Western blot analysis revealed increased amounts of OPA1 protein with maximum amounts at ~3 days post-treatment. In summary, we provide the first mutation-specific in vitro rescue strategy for OPA1 deficiency using synthetic AONs.
Reduced Erythrocyte Survival in Uremic Patients Under Hemodialysis or Peritoneal Dialysis
2016-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;Recent observations in end-stage renal disease (ESRD)-patients on hemodialysis revealed that anemia is, in part, due to stimulated suicidal erythrocyte death or eryptosis leading to accelerated clearance of circulating erythrocytes. The present study explored whether eryptosis is similarly enhanced in patients on peritoneal dialysis (PD). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Measurements were made in freshly drawn erythrocytes from healthy volunteers (n=38), and ESRD patients on hemodialysis (HD; n=18) or on PD (n=22). Both, HD patients and PD patients suffered from anemia despite increased reticulocyte numbers. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The percentage of phosphatidylserine-exposing erythrocytes was significantly higher in HD patients than in healthy volunteers and significantly higher in PD patients than in healthy volunteers and HD patients. In PD patients, the percentage of phosphatidylserine-exposing erythrocytes was positively correlated with dialysis volume. The increase in phosphatidylserine exposure was in both, HD and PD patients, paralleled by increase of reactive oxygen species and ceramide abundance. In both, HD and PD patients, a positive correlation was observed between the percentage of phosphatidylserine-exposing erythrocytes and both, erythropoietin dosage and the percentage of reticulocytes. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Similar to HD patients, PD patients suffer from enhanced eryptosis, which is paralleled by oxidative stress and enhanced ceramide abundance contributing to the anemia of uremic patients.
A ligand substituted tungsten iodide cluster: luminescence vs. singlet oxygen production
2016-01-01

The cluster (TBA)<sub>2</sub>[W<sub>6</sub>I<sub>8</sub>(CF<sub>3</sub>COO)<sub>6</sub>] shows photoluminescence in the solid state and in solution, and singlet oxygen (a<sup>1</sup>Δ<sub>g</sub>) is generated in the presence of oxygen.
Emotions and Decisions
2016-01-01

For centuries, decision scholars paid little attention to emotions: Decisions were modeled in normative and descriptive frameworks with little regard for affective processes. Recently, however, an “emotions revolution” has taken place, particularly in the neuroscientific study of decision making, putting emotional processes on an equal footing with cognitive ones. Yet disappointingly little theoretical progress has been made. The concepts and processes discussed often remain vague, and conclusions about the implications of emotions for rationality are contradictory and muddled. We discuss three complementary ways to move the neuroscientific study of emotion and decision making from agenda setting to theory building. The first is to use reverse inference as a hypothesis-discovery rather than a hypothesis-testing tool, unless its utility can be systematically quantified (e.g., through meta-analysis). The second is to capitalize on the conceptual inventory advanced by the behavioral science of emotions, testing those concepts and unveiling the underlying processes. The third is to model the interplay between emotions and decisions, harnessing existing cognitive frameworks of decision making and mapping emotions onto the postulated computational processes. To conclude, emotions (like cognitive strategies) are not rational or irrational per se: How (un)reasonable their influence is depends on their fit with the environment.
Acid Sphingomyelinase (ASM) is a Negative Regulator of Regulatory T Cell (Treg) Development
2016-01-01

Background/Aims: Regulatory T cell (Treg) is required for the maintenance of tolerance to various tissue antigens and to protect the host from autoimmune disorders. However, Treg may, indirectly, support cancer progression and bacterial infections. Therefore, a balance of Treg function is pivotal for adequate immune responses. Acid sphingomyelinase (ASM) is a rate limiting enzyme involved in the production of ceramide by breaking down sphingomyelin. Previous studies in T-cells have suggested that ASM is involved in CD28 signalling, T lymphocyte granule secretion, degranulation, and vesicle shedding similar to the formation of phosphatidylserine-exposing microparticles from glial cells. However, whether ASM affects the development of Treg has not yet been described. Methods: Splenocytes, isolated Naive T lymphocytes and cultured T cells were characterized for various immune T cell markers by flow cytometery. Cell proliferation was measured by Carboxyfluorescein succinimidyl ester (CFSE) dye, cell cycle analysis by Propidium Iodide (PI), mRNA transcripts by q-RT PCR and protein expression by Western Blotting respectively. Results: ASM deficient mice have higher number of Treg compared with littermate control mice. In vitro induction of ASM deficient T cells in the presence of TGF-β and IL-2 lead to a significantly higher number of Foxp3+ induced Treg (iTreg) compared with control T-cells. Further, ASM deficient iTreg has less AKT (serine 473) phosphorylation and Rictor levels compared with control iTreg. Ceramide C6 led to significant reduction of iTreg in both ASM deficient and WT mice. The reduction in iTreg leads to induction of IL-1β, IL-6 and IL-17 but not IFN-γ mRNA levels. Conclusion: ASM is a negative regulator of natural and iTreg.
Neuromuscular Plasticity: Disentangling Stable and Variable Motor Maps in the Human Sensorimotor Cortex
2016-01-01

Motor maps acquired with transcranial magnetic stimulation (TMS) are evolving as a biomarker for monitoring disease progression or the effects of therapeutic interventions. High test-retest reliability of this technique for long observation periods is therefore required to differentiate daily or weekly fluctuations from stable plastic reorganization of corticospinal connectivity. In this study, a novel projection, interpolation, and coregistration technique, which considers the individual gyral anatomy, was applied in healthy subjects for biweekly acquired TMS motor maps over a period of twelve weeks. The intraclass correlation coefficient revealed long-term reliability of motor maps with relevant interhemispheric differences. The sensorimotor cortex and nonprimary motor areas of the dominant hemisphere showed more extended and more stable corticospinal connectivity. Long-term correlations of the MEP amplitudes at each stimulation site revealed mosaic-like clusters of consistent corticospinal excitability. The resting motor threshold, centre of gravity, and mean MEPs across all TMS sites, as highly reliable cortical map parameters, could be disentangled from more variable parameters such as MEP area and volume. Cortical TMS motor maps provide high test-retest reliability for long-term monitoring when analyzed with refined techniques. They may guide restorative interventions which target dormant corticospinal connectivity for neurorehabilitation.
Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease
2016-01-01

Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. The inflammatory response in CF is dominated by the activation of the innate immune system. Bacteria and fungi represent the key pathogens chronically colonizing the CF airways. In response, innate immune pattern recognition receptors, expressed by airway epithelial and myeloid cells, sense the microbial threat and release chemoattractants to recruit large numbers of neutrophils into CF airways. However, neutrophils fail to efficiently clear the invading pathogens, but instead release harmful proteases and oxidants and finally cause tissue injury. Here, we summarize and discuss current concepts and controversies in the field of innate immunity in CF lung disease, facing the ongoing questions of whether inflammation is good or bad in CF and how innate immune mechanisms could be harnessed therapeutically.
Bile Acid-Induced Suicidal Erythrocyte Death
2016-01-01

Background/Aims: In nucleated cells, bile acids may activate cation channels subsequently leading to entry of Ca2+. In erythrocytes, increase of cytosolic Ca2+ activity triggers eryptosis, the suicidal death of erythrocytes characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis is triggered by bile duct ligation, an effect partially attributed to conjugated bilirubin. The present study explored, whether bile acids may stimulate eryptosis. Methods: Phosphatidylserine exposing erythrocytes have been identified utilizing annexin V binding, cell volume estimated from forward scatter, cytosolic Ca2+ activity determined using Fluo-3 fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Results: The exposure of human erythrocytes to glycochenodesoxycholic (GCDC) and taurochenodesoxycholic (TCDC) acid was followed by a significant decrease of forward scatter and significant increase of Fluo-3 fluorescence, ceramide abundance as well as annexin V binding. The effect on annexin V binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusion: Bile acids stimulate suicidal cell death, an effect paralleled by and in part due to Ca2+ entry and ceramide. The bile acid induced eryptosis may in turn lead to accelerated clearance of circulating erythrocytes and, thus, may contribute to anemia in cholestatic patients.
Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline
2016-01-01

Background/Aims: Several recent clinical studies revealed an accumulation of ceramide in bronchial epithelial cells of patients with cystic fibrosis (CF). Degradation of ceramide concentrations in lungs of CF patients employing the functional acid sphingomyelinase inhibitor amitriptyline revealed a benefit in lung function, weight and exacerbation rates. Methods: To test for a beneficial effect of amitriptyline in vivo, we performed two phase II randomised, double-blind, placebo-controlled studies. CF patients were treated with 25 mg amitriptyline twice daily, i.e. a total dose of 50 mg/d. After those two studies part of the patients used amitriptyline in an off-lable-use for routine treatment. These patients were observed after one, two and three years after continuous use of amitriptyline and were matched with those patients who were not treated. These patients were used as a control group. Results: After one year of treatment, forced expiratory volume in 1 sec predicted (FEV1) increased significantly by 7.6±7.0%, p=&lt;0.001, and weight increased by 2.1±2.3kg, p=&lt;0.001 in the amitriptyline population (n=20), whereas FEV1 decreased significantly in the control group by 1.8±3.3%, p=0.010, and weight increased by 1.1±2.7kg, p=0.010 (n=14). After two years of treatment, FEV1 increased significantly by 5.6±10.3%, p=0.009, and weight increased by 3.6±2.9kg, p=&lt;0.001 in the amitriptyline population (n=12). In contrast, FEV1 decreased in the control group by 2.1±3.7%, p=0.051 and weight increased by only 0.4±2.9kg, p=0.31 (n=10). After three years of treatment, FEV1 increased significantly by 7.7±8%, p=0.050, and weight increased by 7.3±3.8kg, p=0.016, in the amitriptyline population (n=5), whereas FEV1 decreased in the control group by 1.0±1.3%, p=0.075 and weight increased by 0.4±1.5kg, p=0.29 (n=5). Conclusion: Amitriptyline significantly increases FEV1, reduces ceramide in lung cells and increases weight of CF patients.
Resting-state functional MRI in an intraoperative MRI setting: proof of feasibility and correlation to clinical outcome of patients
2016-01-01

OBJECTIVE The authors' aim in this paper is to prove the feasibility of resting-state (RS) functional MRI (fMRI) in an intraoperative setting (iRS-fMRI) and to correlate findings with the clinical condition of patients pre- and postoperatively. METHODS Twelve patients underwent intraoperative MRI-guided resection of lesions in or directly adjacent to the central region and/or pyramidal tract. Intraoperative RS (iRS)–fMRI was performed pre- and intraoperatively and was correlated with patients' postoperative clinical condition, as well as with intraoperative monitoring results. Independent component analysis (ICA) was used to postprocess the RS-fMRI data concerning the sensorimotor networks, and the mean z-scores were statistically analyzed. RESULTS iRS-fMRI in anesthetized patients proved to be feasible and analysis revealed no significant differences in preoperative z-scores between the sensorimotor areas ipsi- and contralateral to the tumor. A significant decrease in z-score (p &lt; 0.01) was seen in patients with new neurological deficits postoperatively. The intraoperative z-score in the hemisphere ipsilateral to the tumor had a significant negative correlation with the degree of paresis immediately after the operation (r = −0.67, p &lt; 0.001) and on the day of discharge from the hospital (r = −0.65, p &lt; 0.001). Receiver operating characteristic curve analysis demonstrated moderate prognostic value of the intraoperative z-score (area under the curve 0.84) for the paresis score at patient discharge. CONCLUSIONS The use of iRS-fMRI with ICA-based postprocessing and functional activity mapping is feasible and the results may correlate with clinical parameters, demonstrating a significant negative correlation between the intensity of the iRS-fMRI signal and the postoperative neurological changes.
The Relationships Between the Dark Triad, the Moral Judgment Level, and the Students’ Disciplinary Choice
2016-01-01

Abstract. The purpose of the present study was to examine the relationships between the personality traits of the Dark Triad, the moral judgment level, and the students’ disciplinary choice. It was hypothesized that students who major in higher business and management education show higher levels of the Dark Triad and lower levels of moral judgment competence (self-selection hypothesis). According to the indoctrination hypothesis it was assumed that the differences between business and management students and other students would be higher in advanced semesters. The findings suggest that business and management students show higher levels of the Dark Triad but not of moral judgment competence. However, there was no evidence found for a higher difference in advanced students.
Content-Based Image Retrieval (CBIR) in Remote Clinical Diagnosis and Healthcare
2016-01-01

Content-Based Image Retrieval (CBIR) locates, retrieves and displays images alike to one given as a query, using a set of features. It demands accessible data in medical archives and from medical equipment, to infer meaning after some processing. A problem similar in some sense to the target image can aid clinicians. CBIR complements text-based retrieval and improves evidence-based diagnosis, administration, teaching, and research in healthcare. It facilitates visual/automatic diagnosis and decision-making in real-time remote consultation/screening, store-and-forward tests, home care assistance and overall patient surveillance. Metrics help comparing visual data and improve diagnostic. Specially designed architectures can benefit from the application scenario. CBIR use calls for file storage standardization, querying procedures, efficient image transmission, realistic databases, global availability, access simplicity, and Internet-based structures. This chapter recommends important and complex aspects required to handle visual content in healthcare.
LEFTY2 Controls Migration of Human Endometrial Cancer Cells via Focal Adhesion Kinase Activity (FAK) and miRNA-200a
2016-01-01

Background: LEFTY2, a suppressor of cell proliferation, tumor growth, regulator of stemness and embryonic differentiation, is a negative regulator of cancer cell reprogramming. Malignant transformation may lead to migration requiring loss of adhesion and gain of migratory activity. Signaling involved in the orchestration of migration, proliferation and spreading of cells include focal adhesion kinase (FAK) and adhesion molecule E-cadherin. Aims: The present study explored whether LEFTY2 influences the proliferation marker MKi67, FAK activity, E-cadherin abundance and migration of Ishikawa human endometrial carcinoma cells. Moreover, the study explored the involvement of microRNA-200a (miR-200a), which is known to regulate cellular adhesion by targeting E-Cadherin. Methods: FAK activity was estimated from FAK phosphorylation quantified by Western blotting, migration utilizing a wound healing assay, miR-200a and MKi67 expression levels utilizing qRT-PCR, cell proliferation and apoptosis using BrdU and Annexin V staining, respectively, and E-Cadherin (E-Cad) abundance, using confocal microscopy. Results: LEFTY2 (25 ng/ml, 48 hours) treatment was followed by decrease of MKi67 expression, FAK activity and migration. LEFTY2 upregulated miRNA-200a and E-Cad protein level in Ishikawa cells. The effect of LEFTY2 on migration was mimicked by FAK inhibitor PF 573228 (50 μM). Addition of LEFTY2 in the presence of PF-573228 did not result in a further significant decline of migration. Conclusion: In conclusion, LEFTY2 down-regulates MKi67 expression and FAK activity, up-regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of endometrial cell proliferation and migration.