Rheotaxis facilitates upstream navigation of mammalian sperm cells

A major puzzle in biology is how mammalian sperm determine and maintain the correct swimming direction during the various phases of the sexual reproduction process. Whilst chemotaxis is assumed to dominate in the immediate vicinity of the ovum, it is unclear which biochemical or physical cues guide spermatozoa on their long journey towards the egg cell. Currently debated mechanisms range from peristaltic pumping to temperature sensing (thermotaxis) and direct response to fluid flow variations (rheotaxis), but little is known quantitatively about their relative importance. Here, we report the first quantitative experimental study of mammalian sperm rheotaxis. Using microfluidic devices, we investigate systematically the swimming behavior of human and bull sperm over the whole range of physiologically relevant shear rates and viscosities. Our measurements show that the interplay of fluid shear, steric surface-interactions and chirality of the flagellar beat leads to a stable upstream spiraling motion of sperm cells, thus providing a generic and robust rectification mechanism to support mammalian fertilisation. To rationalise these findings, we identify a minimal mathematical model that is capable of describing quantitatively the experimental observations. The combined experimental and theoretical evidence supports the hypothesis that the shape and beat patterns of mammalian sperm cells have evolved to optimally exploit rheotaxis for long-distance navigation.Comment: 18 pages, 4 figures, supplementary information available at eLifesciences.or

Gauge-Gravity Dualities, Dipoles and New Non-Kahler Manifolds

In this work we explore many directions in the framework of gauge-gravity dualities. In type IIB theory we give an explicit derivation of the local metric for five branes wrapped on rigid two-cycles. Our derivation involves various interplays between warp factors, dualities and fluxes and the final result confirms our earlier predictions. We also find a novel dipole-like deformation of the background due to an inherent orientifold projection in the full global geometry. The supergravity solution for this deformation takes into account various things like the presence of a non-trivial background topology and fluxes as well as branes. Considering these, we manage to calculate the precise local solution using equations of motion. We also show that this dipole-like deformation has the desired property of decoupling the Kaluza-Klein modes from the IR gauge theory. Finally, for the heterotic theory we find new non-Kahler complex manifolds that partake in the full gauge-gravity dualities and study the mathematical structures of these manifolds including the torsion classes, Betti numbers and other topological data.Comment: Harvmac, 80 pages, 4 .eps figures; v2: Some typos corrected and new references added; v3: More typos corrected and references updated. Final version to appear in Nucl. Phys.

Signal Propagation in Feedforward Neuronal Networks with Unreliable Synapses

In this paper, we systematically investigate both the synfire propagation and firing rate propagation in feedforward neuronal network coupled in an all-to-all fashion. In contrast to most earlier work, where only reliable synaptic connections are considered, we mainly examine the effects of unreliable synapses on both types of neural activity propagation in this work. We first study networks composed of purely excitatory neurons. Our results show that both the successful transmission probability and excitatory synaptic strength largely influence the propagation of these two types of neural activities, and better tuning of these synaptic parameters makes the considered network support stable signal propagation. It is also found that noise has significant but different impacts on these two types of propagation. The additive Gaussian white noise has the tendency to reduce the precision of the synfire activity, whereas noise with appropriate intensity can enhance the performance of firing rate propagation. Further simulations indicate that the propagation dynamics of the considered neuronal network is not simply determined by the average amount of received neurotransmitter for each neuron in a time instant, but also largely influenced by the stochastic effect of neurotransmitter release. Second, we compare our results with those obtained in corresponding feedforward neuronal networks connected with reliable synapses but in a random coupling fashion. We confirm that some differences can be observed in these two different feedforward neuronal network models. Finally, we study the signal propagation in feedforward neuronal networks consisting of both excitatory and inhibitory neurons, and demonstrate that inhibition also plays an important role in signal propagation in the considered networks.Comment: 33pages, 16 figures; Journal of Computational Neuroscience (published

Dipole-Deformed Bound States and Heterotic Kodaira Surfaces

We study a particular N = 1 confining gauge theory with fundamental flavors realised as seven branes in the background of wrapped five branes on a rigid two-cycle of a non-trivial global geometry. In parts of the moduli space, the five branes form bound states with the seven branes. We show that in this regime the local supergravity solution is surprisingly tractable, even though the background topology is non-trivial. New effects such as dipole deformations may be studied in detail, including the full backreactions. Performing the dipole deformations in other ways leads to different warped local geometries. In the dual heterotic picture, which is locally given by a C* fibration over a Kodaira surface, we study details of the geometry and the construction of bundles. We also point out the existence of certain exotic bundles in our framework.Comment: 40 pages, 3 .eps figures, Harvma

Child maltreatment in the "children of the nineties" : a cohort study of risk factors

Aim: To analyze the multiple factors affecting the risk of maltreatment in young children within a comprehensive theoretical framework. Methods: The research is based on a large UK cohort study, the Avon Longitudinal Study of Parents and Children. Out of 14,256 children participating in the study, 293 were investigated by social services for suspected maltreatment and 115 were placed on local child protection registers prior to their 6th birthday. Data on the children have been obtained from obstetric data and from a series of parental questionnaires administered during pregnancy and the first 3 years of life. Risk factors have been analyzed using an hierarchical approach to logistic regression analysis. Results: In the stepwise hierarchical analysis, young parents, those with low educational achievement, and those with a past psychiatric history or a history of childhood abuse were all more likely to be investigated for maltreatment, or to have a child placed on the child protection register, with odds ratios between 1.86 and 4.96 for registration. Examining strength of effect, the highest risks were found with indicators of deprivation (3.24 for investigation and 11.02 for registration, after adjusting for parental background factors). Poor social networks increased the risk of both investigation (adjusted OR 1.93) and registration (adjusted OR 1.90). Maternal employment seemed to reduce the risk of both outcomes but adjusted odds ratios were no longer significant for registration. After adjusting for higher order confounders, single parents and reordered families were both at higher risk of registration. Reported domestic violence increased the risk of investigation and registration but this was no longer significant after adjusting for higher order variables. Low birthweight children were at higher risk of registration as were those whose parents reported few positive attributes of their babies. Conclusions: This study supports previous research in the field demonstrating that a wide range of factors in the parental background, socio-economic and family environments affect the risk of child maltreatment. By combining factors within a comprehensive ecological framework, we have demonstrated that the strongest risks are from socio-economic deprivation and from factors in the parents' own background and that parental background factors are largely, but not entirely, mediated through their impact on socio-economic factors

Validation of serum IGF-I as a biomarker to monitor the bioactivity of exogenous growth hormone agonists and antagonists in rabbits

The development of new growth hormone (GH) agonists and growth hormone antagonists (GHAs) requires animal models for pre-clinical testing. Ideally, the effects of treatment are monitored using the same pharmacodynamic marker that is later used in clinical practice. However, intact rodents are of limited value for this purpose because serum IGF-I, the most sensitive pharmacodynamic marker for the action of GH in humans, shows no response to treatment with recombinant human GH and there is little evidence for the effects of GHAs, except when administered at very high doses or when overexpressed. As an alternative, more suitable model, we explored pharmacodynamic markers of GH action in intact rabbits. We performed the first validation of an IGF-I assay for the analysis of rabbit serum and tested precision, sensitivity, linearity and recovery using an automated human IGF-I assay (IDS-iSYS). Furthermore, IGF-I was measured in rabbits of different strains, age groups and sexes, and we monitored IGF-I response to treatment with recombinant human GH or the GHA Pegvisomant. For a subset of samples, we used LC-MS/MS to measure IGF-I, and quantitative western ligand blot to analyze IGF-binding proteins (IGFBPs). Although recovery of recombinant rabbit IGF-I was only 50% in the human IGF-I assay, our results show that the sensitivity, precision (1.7–3.3% coefficient of variation) and linearity (90.4–105.6%) were excellent in rabbit samples. As expected, sex, age and genetic background were major determinants of IGF-I concentration in rabbits. IGF-I and IGFBP-2 levels increased after single and multiple injections of recombinant human GH (IGF-I: 286±22 versus 434±26 ng/ml; P<0.01) and were highly correlated (P<0.0001). Treatment with the GHA lowered IGF-I levels from the fourth injection onwards (P<0.01). In summary, we demonstrated that the IDS-iSYS IGF-I immunoassay can be used in rabbits. Similar to rodents, rabbits display variations in IGF-I depending on sex, age and genetic background. Unlike in rodents, the IGF-I response to treatment with recombinant human GH or a GHA closely mimics the pharmacodynamics seen in humans, suggesting that rabbits are a suitable new model to test human GH agonists and antagonists

Episodes of intensified biological productivity in the subtropical Atlantic Ocean during the termination of the Middle Eocene Climatic Optimum (MECO)

The Middle Eocene Climatic Optimum (MECO) is an ~500 kyr interval of pronounced global warming from which the climate system recovered in <50 kyr. The deep-sea sedimentary record can provide valuable insight on the marine ecosystem response to this protracted global warming event and consequently on the ecological changes during this time. Here we present new benthic foraminiferal assemblage data from Ocean Drilling Program Site 1051 in the subtropical North Atlantic, spanning the MECO and post-MECO interval (41.1 to 39.5 Ma). We ␣nd little change in the species composition of benthic foraminiferal assemblages during the studied interval, suggesting that the rate of environmental change was gradual enough that these organisms were able to adapt. However, we identify two transient intervals associated with peak warming (higher-productivity interval (HPI)-1; 40.07–39.96 Ma) and shortly after the MECO (HPI-2; 39.68–39.55 Ma), where benthic foraminiferal accumulation rates increase by an order of magnitude. These HPIs at Site 1051 appear to coincide with intervals of strengthened productivity in the Tethys, Southern Ocean, and South Atlantic, and we suggest that an intensi␣ed hydrological cycle during the climatic warmth of the MECO was responsible for eutrophication of marine shelf and slope environments

Geometric Transitions on non-Kaehler Manifolds

This article is based on the author's PhD--thesis. We study geometric transitions on the supergravity level using the basic idea of arXiv:hep-th/0403288, where a pair of non-Kaehler backgrounds was constructed, which are related by a geometric transition. Here we embed this idea into an orientifold setup as suggested in arXiv:hep-th/0511099. The non-Kaehler backgrounds we obtain in type IIA are non-trivially fibered due to their construction from IIB via T-duality with Neveu-Schwarz flux. We demonstrate that these non-Kaehler manifolds are not half-flat and show that a symplectic structure exists on them at least locally. We also review the construction of new non-Kaehler backgrounds in type I and heterotic theory as proposed in arXiv:hep-th/0408192. They are found by a series of T- and S-duality and can be argued to be related by geometric transitions as well. A local toy model is provided that fulfills the flux equations of motion in IIB and the torsional relation in heterotic theory, and that is consistent with the U-duality relating both theories. For the heterotic theory we also propose a global solution that fulfills the torsional relation because it is similar to the Maldacena-Nunez background.Comment: 127 pages, based on PhD-thesis, v2 some references added, this version to appear in Fort. Phy