julilili42/papers huggingface dataset:
Potential Stemness of Frozen-Thawed Testicular Biopsies without Sperm in Infertile Men Included into theIn VitroFertilization Programme
2012-01-01

We describe the potential stemness of a small amount of frozen-thawed testicular tissue without sperm obtained by biopsy from six patients undergoing assisted reproductive treatment. The patients were diagnosed with Sertoli Cell-Only Syndrome alone or combined with maturation arrest. Trying to provide the natural stem cell niche for cultured stem cells, all isolated cells from enzymatically degraded biopsies where cultured together in different culture media and the presence of putative mesenchymal and putative pluripotent ES-like stem cells was indicated using different methods. High throughput real-time quantitative PCR followed by multivariate analysis revealed the formation of distinct cell clusters reflecting high degree of similarity and some of these cell clusters expressed the genes characteristic for pluripotent stem cells. In the presence of the follicular fluid, prepared as serum, putative testicular stem cells showed a certain degree of plasticity, and spontaneously differentiated into adipose-like and neuronal-like cells. Additionally, using differentiation protocols putative testicular stem cells were differentiated into neuronal- and pancreatic-like cells. This study shows that in assisted reproduction programmes, testicular tissue with no sperm might be an important source of stem cells, although it is discarded in daily medical practice; this requires further research.
A hypervalent iodine-mediated spirocyclization of 2-(4-hydroxybenzamido)acrylates – unexpected formation of δ-spirolactones
2012-01-01

On the way towards a new total synthesis of (S)-arogenate, a novel aryl-λ(3)-iodane-mediated oxidative spirocyclization of para-substituted phenol derivatives has been discovered. Starting from easy accessible 2-(4-hydroxybenzamido)acrylates we could construct spirocyclic lactams in up to 52% yield. Under alternative reaction conditions the same precursors underwent an unexpected oxidative spirocyclization yielding a novel δ-spirolactone in up to 70% yield.
On a Tree and a Path with no Geometric Simultaneous Embedding
2012-01-01

Two graphs G1 = (V, E1) and G2 = (V, E2) admit a geometric simultaneous embedding if there exists a set of points P and a bijection M : P → V that induce planar straight-line embeddings both for G1 and for G2.While it is known that two caterpillars always admit a geometric simultaneous embedding and that two trees not always admit one, the question about a tree and a path is still open and is often regarded as the most prominent open problem in this area.We answer this question in the negative by providing a counterexample.Additionally, since the counterexample uses disjoint edge sets for the two graphs, we also negatively answer another open question, that is, whether it is possible to simultaneously embed two edge-disjoint trees.As a final result, we study the same problem when some constraints on the tree are imposed.Namely, we show that a tree of depth 2 and a path always admit a geometric simultaneous embedding.In fact, such a strong constraint is not so far from closing the gap with the instances not admitting any solution, as the tree used in our counterexample has depth 4.
Cycle Killer...Qu'est-ce que c'est? On the Comparative Approximability of Hybridization Number and Directed Feedback Vertex Set
2012-01-01

We show that the problem of computing the hybridization number of two rooted binary phylogenetic trees on the same set of taxa X has a constant factor polynomial-time approximation if and only if the problem of computing a minimum-size feedback vertex set in a directed graph (DFVS) has a constant factor polynomial-time approximation. The latter problem, which asks for a minimum number of vertices to be removed from a directed graph to transform it into a directed acyclic graph, is one of the problems in Karp's seminal 1972 list of 21 NP-complete problems. However, despite considerable attention from the combinatorial optimization community it remains to this day unknown whether a constant factor polynomial-time approximation exists for DFVS. Our result thus places the (in)approximability of hybridization number in a much broader complexity context, and as a consequence we obtain that hybridization number inherits inapproximability results from the problem Vertex Cover. On the positive side, we use results from the DFVS literature to give an O(log r log log r) approximation for hybridization number, where r is the value of an optimal solution to the hybridization number problem.
Functional deficits and morphological changes in the neurogenic bladder match the severity of spinal cord compression
2012-01-01

Following spinal cord injury (SCI), loss of spinal and supraspinal control results in desynchronisation of detrusor vesicae (parasympathicus) and external urethral sphincter (sympathicus) activity. Despite recovery of lower urinary tract function being a high priority in patients with SCI, effective treatment options are unavailable largely because mechanisms are poorly understood. Purpose and methods: We used a clinically relevant model of thoracic SCI compression injury in adult female Wistar rats and confirmed that lesion volumes following severe injuries were significantly greater compared to moderate injuries (p &lt; 0.05). Between 1–9 weeks, we assessed recovery of bladder function as well as return of locomotor function using the Basso, Beattie and Bresnahan (BBB) score. Bladder morphometrics and overall intramural innervation patterns, as assessed with ß-III tubulin immunohistochemistry, were also examined. Results: Despite variability, bladder function was significantly worse following severe compared to moderate compression injury (p &lt; 0.05); furthermore, the degree of bladder and locomotor dysfunction were significantly correlated (r = 0.59; p &lt; 0.05). In addition, at 9 weeks after SCI we saw significantly greater increases in bladder dry weight (p &lt; 0.05) and wall thickness following severe compared to moderate injury as well as increases in intramural axon density (moderate: 3× normal values; severe 5×; both p &lt; 0.05) that also correlated with injury severity (r = 0.89). Conclusion: The moderate and severe compression models show consistent and correlated deficits in bladder and locomotor function, as well as in gross anatomical and histopathological changes. Increased intramural innervation may contribute to neurogenic detrusor overactivity and suggests the use of therapeutic agents which block visceromotoric efferents.
Orthotopic Liver Transplantation in Human-Immunodeficiency-Virus-Positive Patients in Germany
2012-01-01

Objectives . This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods . Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results . 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (), hepatitis B (HBV) (), multiple viral infections of the liver () and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41–86 months). 6 patients had died in the early post-transplantation period from septicaemia (), primary graft dysfunction (), and intrathoracal hemorrhage (). Later on 7 patients had died from septicaemia (), delayed graft failure (), recurrent HCC (), and renal failure (). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions . Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT.
Too Good to be True? Ideomotor Theory from a Computational Perspective
2012-01-01

In recent years, Ideomotor Theory has regained widespread attention and sparked the development of a number of theories on goal-directed behavior and learning. However, there are two issues with previous studies' use of Ideomotor Theory. Although Ideomotor Theory is seen as very general, it is often studied in settings that are considerably more simplistic than most natural situations. Moreover, Ideomotor Theory's claim that effect anticipations directly trigger actions and that action-effect learning is based on the formation of direct action-effect associations is hard to address empirically. We address these points from a computational perspective. A simple computational model of Ideomotor Theory was tested in tasks with different degrees of complexity. The model evaluation showed that Ideomotor Theory is a computationally feasible approach for understanding efficient action-effect learning for goal-directed behavior if the following preconditions are met: (1) The range of potential actions and effects has to be restricted. (2) Effects have to follow actions within a short time window. (3) Actions have to be simple and may not require sequencing. The first two preconditions also limit human performance and thus support Ideomotor Theory. The last precondition can be circumvented by extending the model with more complex, indirect action generation processes. In conclusion, we suggest that Ideomotor Theory offers a comprehensive framework to understand action-effect learning. However, we also suggest that additional processes may mediate the conversion of effect anticipations into actions in many situations.
Elevated Angiopoietin-1 Serum Levels in Patients with Alzheimer’s Disease
2012-01-01

Background . Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles and by massive neuronal loss in the brain. There is epidemiologic and pathologic evidence that AD is associated with vascular risk factors and vascular diseases, contributing to cerebral hypoperfusion with consecutive stimulation of angiogenesis and upregulation of proangiogenic factors such as Angiopoietin-1 (Ang-1). Methods . In the present study, we measured Ang-1 serum levels in 42 patients with AD, 20 patients with mild cognitive impairment (MCI), and in 40 healthy elderly controls by ELISA. Results . We found significantly increased Ang-1 serum levels in patients with AD compared to control subjects<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mrow><mml:mo stretchy="false">(</mml:mo><mml:mrow><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.003</mml:mn></mml:mrow><mml:mo stretchy="false">)</mml:mo></mml:mrow></mml:mrow></mml:math>. There was no significant difference between MCI patients and healthy controls<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mo stretchy="false">(</mml:mo><mml:mrow><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.553</mml:mn></mml:mrow><mml:mo stretchy="false">)</mml:mo></mml:mrow></mml:math>or between AD and MCI patients<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mrow><mml:mo stretchy="false">(</mml:mo><mml:mrow><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.054</mml:mn></mml:mrow><mml:mo stretchy="false">)</mml:mo></mml:mrow></mml:math>. The degree of cognitive impairment as measured by the mini-mental status examination (MMSE) score was significantly correlated with the Ang-1 serum levels in all patients and healthy controls. Conclusions . We found significantly increased Ang-1 serum levels in AD patients. We could also show an association between Ang-1 serum levels and the cognitive status in all patients and healthy controls. Thus, serum Ang-1 could be a potential candidate for a biomarker panel for AD diagnosis.
Palaeoclimate Estimates for Selected Leaf Floras from the Late Pliocene (Reuverian) of Central Europe Based on Different Palaeobotanical Techniques
2012-01-01

To provide quantitative palaeoclimate estimates based on different palaeobotanical techniques for three contemporaneous Pliocene leaf floras, we applied the Coexistence Approach (CoA), leaf margin analysis (LMA), the Climate Leaf Analysis Multivariate Program (CLAMP) and the European Leaf Physiognomic Approach (ELPA). Furthermore, we compared recently published estimates from an additional locality with our data. The leaf physiognomic techniques yield lower mean annual temperatures than the CoA, which is most likely caused by taphonomic biases. Due to these potential biases we are in favour of the CoA as the most reliable method, and its palaeotemperature estimates show similar temperatures for all localities. These estimates are also in good agreement with previously published data derived from other techniques for other Late Pliocene floras from Western and Central Europe. No longitudinal/latitudinal temperature gradient can be observed for the sites under study.
How Facilitation May Interfere with Ecological Speciation
2012-01-01

Compared to the vast literature linking competitive interactions and speciation, attempts to understand the role of facilitation for evolutionary diversification remain scarce. Yet, community ecologists now recognize the importance of positive interactions within plant communities. Here, we examine how facilitation may interfere with the mechanisms of ecological speciation. We argue that facilitation is likely to (1) maintain gene flow among incipient species by enabling cooccurrence of adapted and maladapted forms in marginal habitats and (2) increase fitness of introgressed forms and limit reinforcement in secondary contact zones. Alternatively, we present how facilitation may favour colonization of marginal habitats and thus enhance local adaptation and ecological speciation. Therefore, facilitation may impede or pave the way for ecological speciation. Using a simple spatially and genetically explicit modelling framework, we illustrate and propose some first testable ideas about how, when, and where facilitation may act as a cohesive force for ecological speciation. These hypotheses and the modelling framework proposed should stimulate further empirical and theoretical research examining the role of both competitive and positive interactions in the formation of incipient species.
Interstitial Granulomatous Dermatitis With Arthritis Responding to Tocilizumab
2012-01-01

A 68-year-old man was referred with interstitial granulomatous dermatitis with arthritis involving a large area of his skin. Different treatment approaches remained unsuccessful. Finally, we initiated a treatment with tocilizumab. The response was promising.
Parasite-Specific IL-17-Type Cytokine Responses and Soluble IL-17 Receptor Levels in Alveolar Echinococcosis Patients
2012-01-01

Alveolar Echinococcosis (AE) caused by the cestode Echinococcus multilocularis , is a severe helminth infection of man, where unrestricted parasite growth will ultimately result in organ failure and fatality. The tissue-infiltrative growth of the larval metacestode and the limited efficacy of available drugs complicate successful intervention in AE; patients often need life-long medication, and if possible, surgical resection of affected tissues and organs. Resistance to AE has been reported, but the determinants which confer protection are not known. ln this study, we analyzed in patients at distinct stages of Alveolar Echirococcosis, that is cured, stable and progressive AE, as well as in infection-free controls, the cellular production and plasma levels of pro-inflammatory cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA) and IL-17RB (sIL-17RB). Significantly elevated levels of IL-17B and slL-17RB were observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly, the cellular production of lL-17F and slL-L7RA in response to E. multilocularis antigens was low in AE patients, while levels of slL-17RB were highly enhanced. These observations suggest immune-modulating properties of E. multitocularis on lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate the tissue infiltrative growth of the parasite and its persistence in the human host.
Effect of Thymoquinone on Cytosolic pH and Na<sup>+</sup>/H<sup>+</sup> Exchanger Activity in Mouse Dendritic Cells
2012-01-01

The anti-inflammatory Nigella sativa component thymoquinone compromises the function of dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. DC function is regulated by the Na(+)/H(+) exchanger (NHE), which is stimulated by lipopolysaccharides (LPS) and required for LPS-induced cell swelling, reactive oxygen species (ROS) production, TNF-α release and migration. Here we explored, whether thymoquinone influences NHE activity in DCs. To this end, bone marrow derived mouse DCs were treated with LPS in the absence and presence of thymoquinone (10 μM). Cytosolic pH (pH(i)) was determined from 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from the Na(+)-dependent realkalinization following an ammonium pulse, cell volume from forward scatter in FACS analysis, ROS production from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, TNF-α production utilizing ELISA and DC migration with transwell migration assays. As a result, exposure of DCs to LPS (1 μg/ml) led within 4 hours to transient increase of NHE activity. Thymoquinone did not significantly modify cytosolic pH or cellular NHE activity in the absence of LPS, but abrogated the effect of LPS on NHE activity. Accordingly, in the presence of thymoquinone LPS-treatment resulted in cytosolic acidification. LPS further increased forward scatter and ROS formation, effects similarly abrogated by thymoquinone. Again, in the absence of LPS, thymoquinone did not significantly modify ROS formation and cell volume. LPS further triggered TNF-α release and migration, effects again blunted in the presence of thymoquinone. NHE1 inhibitor cariporide (10 μM) blunted LPS induced TNF-α release and migration. The effects of thymoquinone on NHE activity and migration were reversed upon treatment of the cells with t-butyl hydroperoxide (TBOOH, 5 μM). In conclusion, thymoquinone blunts LPS induced NHE activity, cell swelling, oxidative burst, cytokine release and migration of bone marrow derived murine dendritic cells. NHE inhibition may thus contribute to the antiinflammatory action of thymoquinone.
Rapamycin Sensitive ROS Formation and Na+/H+Exchanger Activity in Dendritic Cells
2012-01-01

Rapamycin, a widely used immunosuppressive drug, has been shown to interfere with the function of dendritic cells (DCs), antigen-presenting cells contributing to the initiation of primary immune responses and the establishment of immunological memory. DC function is governed by the Na(+)/H(+) exchanger (NHE), which is activated by bacterial lipopolysaccharides (LPS) and is required for LPS-induced cell swelling, reactive oxygen species (ROS) production and TNF-α release. The present study explored, whether rapamycin influences NHE activity and/or ROS formation in DCs. Mouse DCs were treated with LPS in the absence and presence of rapamycin (100 nM). ROS production was determined from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, cytosolic pH (pH(i)) from 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from the Na(+)-dependent realkalinization following an ammonium pulse, cell volume from forward scatter in FACS analysis, and TNF-α production utilizing ELISA. In the absence of LPS, rapamycin did not significantly modify cytosolic pH, NHE activity or cell volume but significantly decreased ROS formation. LPS stimulated NHE activity, enhanced forward scatter, increased ROS formation, and triggered TNF-α release, effects all blunted in the presence of rapamycin. NADPH oxidase inhibitor Vas-2870 (10 μM) mimicked the effect of rapamycin on LPS induced stimulation of NHE activity and TNF-α release. The effect of rapamycin on TNF-α release was also mimicked by the antioxidant ROS scavenger Tempol (30 μM) and partially reversed by additional application of tert-butylhydroperoxide (10 μM). In conclusion, in DCs rapamycin disrupts LPS induced ROS formation with subsequent inhibition of NHE activity, cell swelling and TNF-α release.
Conflict Processing in the Rat Brain: Behavioral Analysis and Functional μPET Imaging Using [18F]Fluorodeoxyglucose
2012-01-01

Conflicts in spatial stimulus-response tasks occur when the task-relevant feature of a stimulus implies a response toward a certain location which does not match the location of stimulus presentation. This conflict leads to increased error rates and longer reaction times, which has been termed Simon effect. A model of dual route processing (automatic and intentional) of stimulus features has been proposed, predicting response conflicts if the two routes are incongruent. Although there is evidence that the prefrontal cortex, notably the anterior cingulate cortex (ACC), plays a crucial role in conflict processing, the neuronal basis of dual route architecture is still unknown. In this study, we pursue a novel approach using positron emission tomography (PET) to identify relevant brain areas in a rat model of an auditory Simon task, a neuropsychological interference task, which is commonly used to study conflict processing in humans. For combination with PET we used the metabolic tracer [(18)F]fluorodeoxyglucose, which accumulates in metabolically active brain cells during the behavioral task. Brain areas involved in conflict processing are supposed to be activated when automatic and intentional route processing lead to different responses (dual route model). Analysis of PET data revealed specific activation patterns for different task settings applicable to the dual route model as established for response conflict processing. The rat motor cortex (M1) may be part of the automatic route or involved in its facilitation, while premotor (M2), prelimbic, and ACC seemed to be essential for inhibiting the incorrect, automatic response, indicating conflict monitoring functions. Our findings and the remarkable similarities to the pattern of activated regions reported during conflict processing in humans demonstrate that our rodent model opens novel opportunities to investigate the anatomical basis of conflict processing and dual route architecture.
Induction of Programmed Erythrocyte Death by Gambogic Acid
2012-01-01

Gambogic acid, a xanthone from Garcinia hanburyi, stimulates apoptosis and has thus anticancer potency. Similar to apoptosis of nucleated cells, erythrocytes may undergo apoptosis-like suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the cell surface. Eryptosis could be triggered by increase of cytosolic Ca(2+)-activity ([Ca(2+)](i)), ceramide formation, ATP-depletion and caspase activation. The present study explored, whether gambogic acid triggers eryptosis of human erythrocytes. [Ca(2+)](i )was estimated utilizing Fluo-3 fluorescence, cell volume from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, ceramide abundance utilizing antibodies, and cytosolic ATP with luciferin- luciferase. A 48 h exposure to gambogic acid (500 nM) significantly increased [Ca(2+)](i), stimulated ceramide formation, decreased forward scatter and increased annexin-V-binding. Gambogic acid exposure was followed by a slight but significant increase of hemolysis. Gambogic acid did not significantly modify cytosolic ATP-concentration. Removal of extracellular Ca(2+) slightly, but significantly blunted the effect of gambogic acid (500 nM) on annexin-V-binding. The present observations disclose a novel effect of gambogic acid, i.e. stimulation of suicidal death of human erythrocytes or eryptosis, paralleled by Ca(2+)-entry, ceramide formation, cell shrinkage and phosphatidylserine-exposure.