Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

Programmability of Chemical Reaction Networks

Motivated by the intriguing complexity of biochemical circuitry within individual cells we study Stochastic Chemical Reaction Networks (SCRNs), a formal model that considers a set of chemical reactions acting on a finite number of molecules in a well-stirred solution according to standard chemical kinetics equations. SCRNs have been widely used for describing naturally occurring (bio)chemical systems, and with the advent of synthetic biology they become a promising language for the design of artificial biochemical circuits. Our interest here is the computational power of SCRNs and how they relate to more conventional models of computation. We survey known connections and give new connections between SCRNs and Boolean Logic Circuits, Vector Addition Systems, Petri Nets, Gate Implementability, Primitive Recursive Functions, Register Machines, Fractran, and Turing Machines. A theme to these investigations is the thin line between decidable and undecidable questions about SCRN behavior

What’s in a surname? Physique, aptitude, and sports type comparisons between Tailors and Smiths

Combined heredity of surnames and physique, coupled with past marriage patterns and trade-specific physical aptitude and selection factors, may have led to differential assortment of bodily characteristics among present-day men with specific trade-reflecting surnames (Tailor vs. Smith). Two studies reported here were partially consistent with this genetic-social hypothesis, first proposed by Bäumler (1980). Study 1 (N = 224) indicated significantly higher self-rated physical aptitude for prototypically strength-related activities (professions, sports, hobbies) in a random sample of Smiths. The counterpart effect (higher aptitude for dexterity-related activities among Tailors) was directionally correct, but not significant, and Tailor-Smith differences in basic physique variables were not significant. Study 2 examined two large datasets (Austria/Germany combined, and UK: N = 7001 and 20532) of men’s national high-score lists for track-and-field events requiring different physiques. In both datasets, proportions of Smiths significantly increased from light-stature over medium-stature to heavy-stature sports categories. The predicted counterpart effect (decreasing prevalences of Tailors along these categories) was not supported. Related prior findings, implicit egotism as an alternative interpretation of the evidence, and directions for further inquiry are discussed in conclusion

Detection, prevalence, and transmission of avian hematozoa in waterfowl at the Arctic/sub-Arctic interface: co-infections, viral interactions, and sources of variation

Background The epidemiology of avian hematozoa at high latitudes is still not well understood, particularly in sub-Arctic and Arctic habitats, where information is limited regarding seasonality and range of transmission, co-infection dynamics with parasitic and viral agents, and possible fitness consequences of infection. Such information is important as climate warming may lead to northward expansion of hematozoa with unknown consequences to northern-breeding avian taxa, particularly populations that may be previously unexposed to blood parasites. Methods We used molecular methods to screen blood samples and cloacal/oropharyngeal swabs collected from 1347 ducks of five species during May-August 2010, in interior Alaska, for the presence of hematozoa, Influenza A Virus (IAV), and IAV antibodies. Using models to account for imperfect detection of parasites, we estimated seasonal variation in prevalence of three parasite genera (Haemoproteus, Plasmodium, Leucocytozoon) and investigated how co-infection with parasites and viruses were related to the probability of infection. Results We detected parasites from each hematozoan genus in adult and juvenile ducks of all species sampled. Seasonal patterns in detection and prevalence varied by parasite genus and species, age, and sex of duck hosts. The probabilities of infection for Haemoproteus and Leucocytozoon parasites were strongly positively correlated, but hematozoa infection was not correlated with IAV infection or serostatus. The probability of Haemoproteus infection was negatively related to body condition in juvenile ducks; relationships between Leucocytozoon infection and body condition varied among host species. Conclusions We present prevalence estimates for Haemoproteus, Leucocytozoon, and Plasmodium infections in waterfowl at the interface of the sub-Arctic and Arctic and provide evidence for local transmission of all three parasite genera. Variation in prevalence and molecular detection of hematozoa parasites in wild ducks is influenced by seasonal timing and a number of host traits. A positive correlation in co-infection of Leucocytozoon and Haemoproteus suggests that infection probability by parasites in one or both genera is enhanced by infection with the other, or that encounter rates of hosts and genus-specific vectors are correlated. Using size-adjusted mass as an index of host condition, we did not find evidence for strong deleterious consequences of hematozoa infection in wild ducks.Geological Survey (U.S.) (Wildlife Program of the Ecosystem Mission Area)U.S. Fish and Wildlife ServiceDelta Waterfowl FoundationInstitute for Wetland and Waterfowl ResearchIcahn School of Medicine at Mount Sinai (Center for Research on Influenza Pathogenesis)Center of Excellence for Influenza Research and Surveillance (contracts HHSN272201400008C and HHSN266200700010C

Genome-scale modeling of the protein secretory machinery in yeast

The protein secretory machinery in Eukarya is involved in post-translational modification (PTMs) and sorting of the secretory and many transmembrane proteins. While the secretory machinery has been well-studied using classic reductionist approaches, a holistic view of its complex nature is lacking. Here, we present the first genome-scale model for the yeast secretory machinery which captures the knowledge generated through more than 50 years of research. The model is based on the concept of a Protein Specific Information Matrix (PSIM: characterized by seven PTMs features). An algorithm was developed which mimics secretory machinery and assigns each secretory protein to a particular secretory class that determines the set of PTMs and transport steps specific to each protein. Protein abundances were integrated with the model in order to gain system level estimation of the metabolic demands associated with the processing of each specific protein as well as a quantitative estimation of the activity of each component of the secretory machinery

Production and transfer of energy and information in Hamiltonian systems

We present novel results that relate energy and information transfer with sensitivity to initial conditions in chaotic multi-dimensional Hamiltonian systems. We show the relation among Kolmogorov-Sinai entropy, Lyapunov exponents, and upper bounds for the Mutual Information Rate calculated in the Hamiltonian phase space and on bi-dimensional subspaces. Our main result is that the net amount of transfer from kinetic to potential energy per unit of time is a power-law of the upper bound for the Mutual Information Rate between kinetic and potential energies, and also a power-law of the Kolmogorov-Sinai entropy. Therefore, transfer of energy is related with both transfer and production of information. However, the power-law nature of this relation means that a small increment of energy transferred leads to a relatively much larger increase of the information exchanged. Then, we propose an ?experimental? implementation of a 1-dimensional communication channel based on a Hamiltonian system, and calculate the actual rate with which information is exchanged between the first and last particle of the channel. Finally, a relation between our results and important quantities of thermodynamics is presented

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Palaeoclimate inferred from δ18O and palaeobotanical indicators in freshwater tufa of Lake Äntu Sinijärv, Estonia

We investigated a 3.75-m-long lacustrine sediment record from Lake Äntu Sinijärv, northern Estonia, which has a modeled basal age >12,800 cal yr BP. Our multi-proxy approach focused on the stable oxygen isotope composition (δ18O) of freshwater tufa. Our new palaeoclimate information for the Eastern Baltic region, based on high-resolution δ18O data (219 samples), is supported by pollen and plant macrofossil data. Radiocarbon dates were used to develop a core chronology and estimate sedimentation rates. Freshwater tufa precipitation started ca. 10,700 cal yr BP, ca. 2,000 years later than suggested by previous studies on the same lake. Younger Dryas cooling is documented clearly in Lake Äntu Sinijärv sediments by abrupt appearance of diagnostic pollen (Betula nana, Dryas octopetala), highest mineral matter content in sediments (up to 90 %) and low values of δ18O (less than −12 ‰). Globally recognized 9.3- and 8.2-ka cold events are weakly defined by negative shifts in δ18O values, to −11.3 and −11.7 ‰, respectively, and low concentrations of herb pollen and charcoal particles. The Holocene thermal maximum (HTM) is palaeobotanically well documented by the first appearance and establishment of nemoral thermophilous taxa and presence of water lilies requiring warm conditions. Isotope values show an increasing trend during the HTM, from −11.5 to −10.5 ‰. Relatively stable environmental conditions, represented by only a small-scale increase in δ18O (up to 1 ‰) and high pollen concentrations between 5,000 and 3,000 cal yr BP, were followed by a decrease in δ18O, reaching the most negative value (−12.7 ‰) recorded in the freshwater tufa ca. 900 cal yr BP

Chironomid-based palaeotemperature estimates for northeast Finland during Oxygen Isotope Stage 3.

Quantitative palaeotemperature estimates for the earlier part of Oxygen Isotope Stage (OIS-) 3 are inferred from subfossil chironomid remains. The high-latitudinal study site of Sokli, northeast Finland, provides for a unique lacustrine deposit covering the earlier part of OIS-3, and the chironomid remains found in the sediments show that a shallow lake with a diverse fauna was present at the study site throughout the record. Using a Norwegian calibration data set as a modern analogue, mean July air temperatures are reconstructed. The chironomid-inferred July air temperatures are surprisingly high, reaching values similar to the current temperature at the study site. Other proxies that were applied to the sediments included the analysis of botanical and zoological macro-remains, and our results concur with temperature estimates derived from climate indicator taxa. Summer temperatures for interstadial conditions, reconstructed with climate models, are as high as our proxy-based palaeotemperatures

Fatigue in low-grade glioma

Contains fulltext : 80675.pdf (publisher's version ) (Closed access)The aim of this study was to determine the prevalence and severity of fatigue in long-term survivors with a low-grade glioma (LGG), and to analyze the relationship between fatigue and demographic variables, disease duration, tumor characteristics, former tumor treatment modalities, antiepileptic drug (AED) use, self-reported concentration, motivation, and activity. Fifty-four patients with stable disease (age range, 25-73 years) who were diagnosed and treated more than 8 years ago were included in this study. Fatigue was analyzed with the Checklist Individual Strength (CIS). Thirty-nine percent of the LGG patients were severely fatigued, with older patients being most affected. Severe fatigue was associated with AED use, and with reduced self-reported concentration, motivation, and activity. No relation was found between fatigue and gender, histology, tumor laterality, disease duration, type of neurosurgical intervention and radiation treatment. Fatigue is a severe problem in a large proportion of long-term surviving LGG patients