julilili42/papers huggingface dataset:
Immunosenescence and Cancer
2013-01-01

The immune system, interacting intimately with the cancer cells in a tumor, may combat or favor cancer development and progression, or both. One of the most important risk factors for solid cancers is age. With increasing age, numerous alterations at multiple levels including molecular, cellular, organ, and systemic are occurring. With age many physiological systems are changing, including the immune system. Several alterations occur in both arms of the immune system with aging. Although the innate immune system shows changes with aging, the most important alterations occur in the adaptive immune system, especially involving T cells. Many changes in the immune system may decrease its capacity to combat the emerging or progressing tumor. Further, the age-related immune changes may favor the cancer development. The most important changes which may decrease the immune response efficiency are the changes in T cell functions and phenotypes, concomitant with the presence of a low-grade inflammation. A consensus is now emerging in oncology that not only the cancer cells themselves should be studied but also their macro- and microenvironments. In this context, the study of the interrelation of the immune response and the tumor at various stages is essential to enhance our capacity for intervention in elderly cancer patients.
Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models
2013-01-01

The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.
Crosstalk between platelets and the complement system in immune protection and disease
2013-01-01

Summary Platelets have a central function in repairing vascular damage and stopping acute blood loss. They are equally central to thrombus formation in cardiovascular diseases such as myocardial infarction and ischaemic stroke. Beyond these classical prothrombotic diseases, immune mediated pathologies such as haemolytic uraemic syndrome (HUS) or paroxysmal nocturnal haemoglobinuria (PNH) also feature an increased tendency to form thrombi in various tissues. It has become increasingly clear that the complement system, part of the innate immune system, has an important role in the pathophysiology of these diseases. Not only does complement influence prothrombotic disease, it is equally involved in idiopathic thrombocytopenic purpura (ITP), an autoimmune disease characterised by thrombocytopenia. Thus, there are complex interrelationships between the haemostatic and immune systems, and platelets and complement in particular. Not only does complement influence platelet diseases such as ITP, HUS and PNH, it also mediates interaction between microbes and platelets during systemic infection, influencing the course of infection and development of protective immunity. This review aims to provide an integrative overview of the mechanisms underlying the interactions between complement and platelets in health and disease.
Age Sensitivity of NFκB Abundance and Programmed Cell Death in Erythrocytes Induced by NFκB Inhibitors
2013-01-01

NFκB protein abundance is lowest and spontaneous eryptosis as well as susceptibility to Bay 11-7082 and parthenolide highest in aged erythrocytes. Thus, inhibition of NFκB signalling alone is not responsible for the stimulation of eryptosis by parthenolide or Bay 11-7082.
Cost-based pragmatic inference about referential expressions
2013-01-01

We present data from three experiments addressing how much theory of mind reasoning is involved in production and interpretation of ambiguous referential expressions in an artificial language task, and how this interacts with the cost and availability of alternative utterances. When an unambiguous alternative is not available, listeners tend to draw simple Quantity inferences reminiscent of scalar implicatures (Grice, 1975). When an unambiguous alternative is available, fewer inferences are observed, but gradiently more as the cost of unambiguous alternatives increase. We outline a novel game theoretic model of pragmatic reasoning based on probabilistic back-and-forth reasoning about interlocutors’ rational choices and beliefs. The model provides a good fit to the data and raises interesting issues for future research.
Archaeal and bacterial diversity in an arsenic-rich shallow-sea hydrothermal system undergoing phase separation
2013-01-01

Phase separation is a ubiquitous process in seafloor hydrothermal vents, creating a large range of salinities. Toxic elements (e.g., arsenic) partition into the vapor phase, and thus can be enriched in both high and low salinity fluids. However, investigations of microbial diversity at sites associated with phase separation are rare. We evaluated prokaryotic diversity in arsenic-rich shallow-sea vents off Milos Island (Greece) by comparative analysis of 16S rRNA clone sequences from two vent sites with similar pH and temperature but marked differences in salinity. Clone sequences were also obtained for aioA-like functional genes (AFGs). Bacteria in the surface sediments (0-1.5 cm) at the high salinity site consisted of mainly Epsilonproteobacteria (Arcobacter sp.), which transitioned to almost exclusively Firmicutes (Bacillus sp.) at ~10 cm depth. However, the low salinity site consisted of Bacteroidetes (Flavobacteria) in the surface and Epsilonproteobacteria (Arcobacter sp.) at ~10 cm depth. Archaea in the high salinity surface sediments were dominated by the orders Archaeoglobales and Thermococcales, transitioning to Thermoproteales and Desulfurococcales (Staphylothermus sp.) in the deeper sediments. In contrast, the low salinity site was dominated by Thermoplasmatales in the surface and Thermoproteales at depth. Similarities in gas and redox chemistry suggest that salinity and/or arsenic concentrations may select for microbial communities that can tolerate these parameters. Many of the archaeal 16S rRNA sequences contained inserts, possibly introns, including members of the Euryarchaeota. Clones containing AFGs affiliated with either Alpha- or Betaproteobacteria, although most were only distantly related to published representatives. Most clones (89%) originated from the deeper layer of the low salinity, highest arsenic site. This is the only sample with overlap in 16S rRNA data, suggesting arsenotrophy as an important metabolism in similar environments.
The temporo-parietal junction contributes to global gestalt perception—evidence from studies in chess experts
2013-01-01

In a recent neuroimaging study the comparison of intact vs. disturbed perception of global gestalt indicated a significant role of the temporo-parietal junction (TPJ) in the intact perception of global gestalt (Huberle and Karnath, 2012). This location corresponded well with the areas known to be damaged or impaired in patients with simultanagnosia after stroke or due to neurodegenerative diseases. It was concluded that the TPJ plays an important role in the integration of individual items to a holistic percept. Thus, increased BOLD signals should be found in this region whenever a task calls for the integration of multiple visual items. Behavioral experiments in chess experts suggested that their superior skills in comparison to chess novices are partly based on fast holistic processing of chess positions with multiple pieces. We thus analyzed BOLD data from four fMRI studies that compared chess experts with chess novices during the presentation of complex chess-related visual stimuli (Bilalić et al., 2010, 2011a,b, 2012). Three regions of interests were defined by significant TPJ clusters in the abovementioned study of global gestalt perception (Huberle and Karnath, 2012) and BOLD signal amplitudes in these regions were compared between chess experts and novices. These cross-paradigm ROI analyses revealed higher signals at the TPJ in chess experts in comparison to novices during presentations of complex chess positions. This difference was consistent across the different tasks in five independent experiments. Our results confirm the assumption that the TPJ region identified in previous work on global gestalt perception plays an important role in the processing of complex visual stimulus configurations.
Estramustine-Induced Suicidal Erythrocyte Death
2013-01-01

Estramustine stimulates both, eryptosis and hemolysis. The estramustine induced translocation of phosphatidylserine to the cell surface is at least partially due to increase of cytosolic Ca2+ activity.
Tannic Acid Induced Suicidal Erythrocyte Death
2013-01-01

Background: The polyphenol tannic acid with antioxidant and antimicrobial potency may trigger suicidal death of nucleated cells or apoptosis and thus may counteract tumor growth. In analogy to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with appearance of phosphatidylserine at the erythrocyte surface. A major trigger of eryptosis is increase of cytosolic Ca2+-activity ([Ca2+]i). Erythrocytes could be sensitized to the eryptotic effect of cytosolic Ca2+ by ceramide. Methods: Cell volume has been estimated from forward scatter, phosphatidylserine abundance at the erythrocyte surface from annexin V binding, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fuorescence and ceramide utilizing fluorescent antibodies. Results: A 48 h treatment with tannic acid was followed by significant decrease of forward scatter (≥ 1 μg/ml) and significant increase of annexin-V-binding (≥ 10 μg/ml). Tannic acid did not significantly modify [Ca2+]i (up to 50 μM) but significantly increased ceramide formation (50 μM). The annexin-V-binding following tannic acid treatment (50 μM) was significantly blunted in the nominal absence of extracellular Ca2+. Conclusions: Tannic acid stimulates eryptosis, an effect at least partially due to ceramide formation with subsequent sensitization of erythrocytes to cytosolic Ca2+.
Down-Regulation of the Na<sup>+</sup>-Coupled Phosphate Transporter NaPi-IIa by AMP-Activated Protein Kinase
2013-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;The Na&lt;sup&gt;+&lt;/sup&gt;-coupled phosphate transporter NaPi-IIa is the main carrier accomplishing renal tubular phosphate reabsorption. It is driven by the electrochemical Na&lt;sup&gt;+&lt;/sup&gt; gradient across the apical cell membrane, which is maintained by Na&lt;sup&gt;+&lt;/sup&gt; extrusion across the basolateral cell membrane through the Na&lt;sup&gt;+&lt;/sup&gt;/K&lt;sup&gt;+&lt;/sup&gt; ATPase. The operation of NaPi-IIa thus requires energy in order to avoid cellular Na&lt;sup&gt;+&lt;/sup&gt; accumulation and K&lt;sup&gt;+&lt;/sup&gt; loss with eventual decrease of cell membrane potential, Cl&lt;sup&gt;-&lt;/sup&gt; entry and cell swelling. Upon energy depletion, early inhibition of Na&lt;sup&gt;+&lt;/sup&gt;-coupled transport processes may delay cell swelling and thus foster cell survival. Energy depletion is sensed by the AMP-activated protein kinase (AMPK), a serine/threonine kinase stimulating several cellular mechanisms increasing energy production and limiting energy utilization. The present study explored whether AMPK influences the activity of NAPi-IIa. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;cRNA encoding NAPi-IIa was injected into &lt;i&gt;Xenopus&lt;/i&gt; oocytes with or without additional expression of wild-type AMPK (AMPK&lt;sup&gt;α1&lt;/sup&gt;-HA+AMPK&lt;sup&gt;β1&lt;/sup&gt;-Flag+AMPK&lt;sup&gt;&amp;#947;1&lt;/sup&gt;-HA), of inactive AMPK&lt;sup&gt;αK45R&lt;/sup&gt; (AMPK&lt;sup&gt;α1K45R&lt;/sup&gt;+AMPK&lt;sup&gt;β1&lt;/sup&gt;-Flag+AMPK&lt;sup&gt;&amp;#947;1&lt;/sup&gt;-HA) or of constitutively active AMPK&lt;sup&gt;&amp;#947;R70Q&lt;/sup&gt; (AMPK&lt;sup&gt;α1&lt;/sup&gt;-HA+AMPK&lt;sup&gt;β1&lt;/sup&gt;-Flag+AMPK&amp;#947;1&lt;sup&gt;R70Q&lt;/sup&gt;). NaPi-IIa activity was estimated from phosphate-induced current in dual electrode voltage clamp experiments. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;In NaPi-IIa-expressing, but not in water-injected &lt;i&gt;Xenopus&lt;/i&gt; oocytes, the addition of phosphate (1 mM) to the extracellular bath solution generated a current (I&lt;sub&gt;p&lt;/sub&gt;), which was significantly decreased by coexpression of wild-type AMPK and of AMPK&lt;sup&gt;&amp;#947;R70Q&lt;/sup&gt; but not of AMPK&lt;sup&gt;αK45R&lt;/sup&gt;. The phosphate-induced current in NaPi-IIa- and AMPK-expressing &lt;i&gt;Xenopus&lt;/i&gt; ooocytes was significantly increased by AMPK inhibitor Compound C (20 μM). Kinetic analysis revealed that AMPK significantly decreased the maximal transport rate. &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;The AMP-activated protein kinase AMPK is a powerful regulator of NaPi-IIa and thus of renal tubular phosphate transport.
Evolutionary and genetic aspects of aphid biology: A review
2013-01-01

In this paper we review recent work on aspects of aphid biology related to evolution and genetics, and suggest some directions for future research. Sections include aphid annual cycles, sexual reproduction, cytogenetics, classical genetics and molecular generics, as well as the influence of annual cycle components on the genetic structure of aphid populations. The related topic of symbiont genome, evolution and function is also briefly reviewed.
Mapping the mechanical stiffness of live cells with the scanning ion conductance microscope
2013-01-01

Mapping the mechanical properties of living cells with high spatial and temporal resolution is important for the exploration of cell function. Widely used imaging techniques such as the atomic force microscope are generally based on direct mechanical contact between the probe and the cell, thereby involving the risk of damaging the cell. Here, we present a noncontact method for fast and quantitative stiffness mapping of living cells with sub-micrometer lateral resolution. This was achieved by repeatedly moving a pressurized nanopipette toward and away from the sample in a scanning ion conductance microscope (SICM). The pressure-induced microfluidic flow through the nanopipette produced a time-varying force on the sample surface, thereby locally indenting it without direct mechanical contact. Maps of sample stiffness (quantified by the Young's modulus) were then determined from ion current approach curves using a finite element model. To demonstrate the capability of the method we visualized the dynamics of individual cytoskeleton fibers in living cells over several hours. Additionally, we found that spreading extensions of migrating fibroblast cells tend to be softer than their lamellum, which is consistent with a mechanism of cell migration by osmotic swelling.
Impact of Pt additives on the surface reactions between SnO2, water vapour, CO and H2; an operando investigation
2013-01-01

The impact of Pt doping on the surface reactions between tin dioxide, water vapour, CO and H2 was investigated by a combination of simultaneously performed operando DRIFT (Diffuse Reflectance Infrared Fourier Transform) spectroscopy, DC resistance measurements and analysis of the reaction products by using a MS (Mass Spectrometer). Both undoped and Pt doped tin dioxide sensors were exposed to different test gases in synthetic air or in N2 backgrounds. The approach made it possible to identify the differences between the two materials with respect to their surface chemistry and their impact on the gas sensing performance. The main finding is that the presence of Pt changes the reaction partners' nature for water vapour and H2 on the one hand, and CO on the other hand when the sensors are operated in air. In this way the cross interference effect of humidity, which is responsible for the loss of CO sensing performance for the sensors based on undoped SnO2, is reversed.
Mcp1 and Mcp2, two novel proteins involved in mitochondrial lipid homeostasis
2013-01-01

The mitochondrial outer membrane (MOM) protein Mdm10 is involved in at least three different processes: (i) association of mitochondria with the endoplasmic reticulum and mitochondrial lipid homeostasis, (ii) membrane assembly of MOM proteins, and (iii) inheritance and morphogenesis of mitochondria. To decipher the precise role of Mdm10 in mitochondrial function, we screened for high-copy suppressors of the severe growth defect of the mdm10Δ mutant. We identified two novel mitochondrial proteins that we named Mdm10 complementing protein (Mcp) 1 and Mcp2. Over-expression of Mcp1 or Mcp2 restores the alterations in morphology and stability of respiratory chain complexes of mitochondria devoid of Mdm10, yet the observed defect in assembly of MOM proteins was not rescued. Lipid analysis demonstrates that elevated levels of Mcp1 and Mcp2 restore the alterations in mitochondrial phospholipid and ergosterol homeostasis in cells lacking Mdm10. Collectively, this work identifies two novel proteins that play a role in mitochondrial lipid homeostasis and describes a role of Mdm10 in ergosterol trafficking.
Unraveling the cellular and molecular mechanisms of repetitive magnetic stimulation
2013-01-01

Despite numerous clinical studies, which have investigated the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) in various brain diseases, our knowledge of the cellular and molecular mechanisms underlying rTMS-based therapies remains limited. Thus, a deeper understanding of rTMS-induced neural plasticity is required to optimize current treatment protocols. Studies in small animals or appropriate in vitro preparations (including models of brain diseases) provide highly useful experimental approaches in this context. State-of-the-art electrophysiological and live-cell imaging techniques that are well established in basic neuroscience can help answering some of the major questions in the field, such as (i) which neural structures are activated during TMS, (ii) how does rTMS induce Hebbian plasticity, and (iii) are other forms of plasticity (e.g., metaplasticity, structural plasticity) induced by rTMS? We argue that data gained from these studies will support the development of more effective and specific applications of rTMS in clinical practice.
Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents
2013-01-01

Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of "how much" information is conveyed by primary afferents, using the direct method (DM), a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s). Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on "what" is coded by primary afferents. Amongst the kinematic variables tested--position, velocity, and acceleration--primary afferent spikes encoded velocity best. The other two variables contributed to information transfer, but only if combined with velocity. We further revealed three additional characteristics that play a role in information transfer by primary afferents. Firstly, primary afferent spikes show preference for well separated multiple stimuli (i.e., well separated sets of combinations of the three instantaneous kinematic variables). Secondly, neurons are sensitive to short strips of the stimulus trajectory (up to 10 ms pre-spike time), and thirdly, they show spike patterns (precise doublet and triplet spiking). In order to deal with these complexities, we used a flexible probabilistic neuron model fitting mixtures of Gaussians to the spike triggered stimulus distributions, which quantitatively captured the contribution of the mentioned features and allowed us to achieve a full functional analysis of the total information rate indicated by the DM. We found that instantaneous position, velocity, and acceleration explained about 50% of the total information rate. Adding a 10 ms pre-spike interval of stimulus trajectory achieved 80-90%. The final 10-20% were found to be due to non-linear coding by spike bursts.
A Review of Cord Blood Concentrations of Iron Status Parameters to Define Reference Ranges for Preterm Infants
2013-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Iron plays an essential role in various tissue functions, and hence the reliable assessment of iron nutrition status of preterm infants appears to be mandatory. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; To summarize available data on cord blood concentrations of iron status parameters as surrogate reference ranges for preterm infants until term-equivalent age. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Review of the literature searching PubMed for cord blood values of hemoglobin, mean corpuscular volume, ferritin, soluble transferrin receptor, ferritin index, transferrin saturation, reticulocyte hemoglobin content, zinc protoporphyrin/heme ratio, and hepcidin and comparison with reference ranges established for adults. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Gestational age-specific cord blood concentration ranges at term were computed as weighted mean for hemoglobin [15.9 g/dl (13.3-18.4)], mean corpuscular volume [108.1 fl (97.8-118.5)] and transferrin saturation [61.2% (31.5-90.9)] and listed for ferritin, soluble transferrin receptor, ferritin index, zinc protoporphyrin/heme ratio, reticulocyte hemoglobin content and hepcidin. These surrogate reference ranges were markedly different from adult values. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Reference ranges of iron status parameters established for adults are probably not suitable to define iron status in preterm infants. If iron supplementation in preterm infants should be individually adjusted based on iron status parameters, it may be necessary to aim for cord blood concentration ranges to enable optimal growth and development.