Dynamics of the formation of a hydrogel by a pathogenic amyloid peptide: islet amyloid polypeptide

Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces. Here we used surface tensiometry, rheology and electron microscopy to demonstrate the complex dynamics of gelation by full-length human islet amyloid polypeptide (involved in type II diabetes) both in the bulk solution and at hydrophobic-hydrophilic interfaces (air-water interface and phospholipids). We show that the hydrogel consists of a 3D supramolecular network of fibrils. We also assessed the role of solvation and dissected the evolution over time of the assembly processes. Amyloid gelation could have important pathological consequences for membrane integrity and cellular functions

Universal Conductance Distribution in the Quantum Size Regime

We study the conductance (g) distribution function of an ensemble of isolated conducting rings, with an Aharonov--Bohm flux. This is done in the discrete spectrum limit, i.e., when the inelastic rate, frequency and temperature are all smaller than the mean level spacing. Over a wide range of g the distribution function exhibits universal behavior P(g)\sim g^{-(4+\beta)/3}, where \beta=1 (2) for systems with (without) a time reversal symmetry. The nonuniversal large g tail of this distribution determines the values of high moments.Comment: 13 pages+1 figure, RevTEX

Drawbacks of ovarian ablation with goserelin in women with breast cancer

In the last few years, ovarian ablation with GnRH agonists has been used as first-line adjuvant therapy in pre and perimenopausal breast cancer. These drugs suppress ovarian function in the hypothalamic-pituitary axis and they have adverse effects in other end-organs. A retrospective study was conducted on 35 premenopausal women, with breast cancer, and treated with goserelin, in order to investigate the effects of iatrogenic estrogen suppression. All women complaint of amenorrhea and only half of them referred hot-flashes, weight gain or arthralgias. Hot-flushes and arthralgias remit spontaneously in the end of the treatment. Osteodensitometry was used to access bone mass. There was a reduction in mineral bone mass and T-score at femoral neck and lumbar spine after the treatment with goserelin, but without statistical significance, except for the T-score in lumbar spine

Genetic variations in androgen metabolism genes and associations with prostate cancer in South African men

Background. In South Africa white men have the highest incidence of prostate cancer (PCa), coloured (mixed ancestry) men have an intermediate incidence, and low incidences are reported for black and Asian men. It has been suggested that ethnic differences in incidence and mortality of PCa are related to genetic variations in genes that regulate androgen metabolism. We investigated the role of genetic variants in the androgen metabolism genes and the probability of developing PCa in South African coloured and white men. Methods. Genotype and allele counts and frequencies of single nucleotide polymorphisms (SNPs) in CYP3A5, CYP3A4 and CYP3A43 were assessed in coloured men (160 case individuals, 146 control individuals) and white men (121 case individuals, 141 control individuals). Results. A genetic association indicating an increased probability of developing PCa was observed with the G allele of the SNP rs2740574 in CYP3A4 in coloured men, the A allele of rs776746 (CYP3A5) and the G allele of rs2740574 (CYP3A4) in white men, and the G allele of rs2740574 and the C allele of rs501275 (CYP3A43) in the combined ethnic groups analysis. In addition, we identified allele combinations (termed haplotypes) with significantly higher frequencies in the PCa case individuals than in the control individuals. Conclusions. The findings support the role of variants in genes that regulate androgen metabolism and the probability of developing PCa. The study paves the way to identify other genetic associations in South African men, and to establish genetic profiles that could be used to determine disease progression and prognosis

Rotating curved spacetime signatures from a giant quantum vortex

\ua9 The Author(s) 2024.Gravity simulators1 are laboratory systems in which small excitations such as sound2 or surface waves3,4 behave as fields propagating on a curved spacetime geometry. The analogy between gravity and fluids requires vanishing viscosity2–4, a feature naturally realized in superfluids such as liquid helium or cold atomic clouds5–8. Such systems have been successful in verifying key predictions of quantum field theory in curved spacetime7–11. In particular, quantum simulations of rotating curved spacetimes indicative of astrophysical black holes require the realization of an extensive vortex flow12 in superfluid systems. Here we demonstrate that, despite the inherent instability of multiply quantized vortices13,14, a stationary giant quantum vortex can be stabilized in superfluid 4He. Its compact core carries thousands of circulation quanta, prevailing over current limitations in other physical systems such as magnons5, atomic clouds6,7 and polaritons15,16. We introduce a minimally invasive way to characterize the vortex flow17,18 by exploiting the interaction of micrometre-scale waves on the superfluid interface with the background velocity field. Intricate wave–vortex interactions, including the detection of bound states and distinctive analogue black hole ringdown signatures, have been observed. These results open new avenues to explore quantum-to-classical vortex transitions and use superfluid helium as a finite-temperature quantum field theory simulator for rotating curved spacetimes19

Rapid planetesimal formation in turbulent circumstellar discs

The initial stages of planet formation in circumstellar gas discs proceed via dust grains that collide and build up larger and larger bodies (Safronov 1969). How this process continues from metre-sized boulders to kilometre-scale planetesimals is a major unsolved problem (Dominik et al. 2007): boulders stick together poorly (Benz 2000), and spiral into the protostar in a few hundred orbits due to a head wind from the slower rotating gas (Weidenschilling 1977). Gravitational collapse of the solid component has been suggested to overcome this barrier (Safronov 1969, Goldreich & Ward 1973, Youdin & Shu 2002). Even low levels of turbulence, however, inhibit sedimentation of solids to a sufficiently dense midplane layer (Weidenschilling & Cuzzi 1993, Dominik et al. 2007), but turbulence must be present to explain observed gas accretion in protostellar discs (Hartmann 1998). Here we report the discovery of efficient gravitational collapse of boulders in locally overdense regions in the midplane. The boulders concentrate initially in transient high pressures in the turbulent gas (Johansen, Klahr, & Henning 2006), and these concentrations are augmented a further order of magnitude by a streaming instability (Youdin & Goodman 2005, Johansen, Henning, & Klahr 2006, Johansen & Youdin 2007) driven by the relative flow of gas and solids. We find that gravitationally bound clusters form with masses comparable to dwarf planets and containing a distribution of boulder sizes. Gravitational collapse happens much faster than radial drift, offering a possible path to planetesimal formation in accreting circumstellar discs.Comment: To appear in Nature (30 August 2007 issue). 18 pages (in referee mode), 3 figures. Supplementary Information can be found at 0708.389

Simple Observables from Fat Link Fermion Actions

A comparison is made of the (quenched) light hadron spectrum and of simple matrix elements for a hypercubic fermion action (based on a fixed point action) and the clover action, both using fat links, at a lattice spacing a= 0.18 fm. Renormalization constants for the naive and improved vector current and the naive axial current are computed using Ward identities. The renormalization factors are very close to unity, and the spectroscopy of light hadrons and the pseudoscalar and vector decay constants agree well with simulations at smaller lattice spacings (and with experiment).Comment: 22 pages, 12 postscript figures, Revtex plus eps

Inaugurating a Dutch Napoleon? Conservative criticism of the 1815 constitution of the United Kingdom of The Netherlands

International audienc

Potentiality in Biology

We take the potentialities that are studied in the biological sciences (e.g., totipotency) to be an important subtype of biological dispositions. The goal of this paper is twofold: first, we want to provide a detailed understanding of what biological dispositions are. We claim that two features are essential for dispositions in biology: the importance of the manifestation process and the diversity of conditions that need to be satisfied for the disposition to be manifest. Second, we demonstrate that the concept of a disposition (or potentiality) is a very useful tool for the analysis of the explanatory practice in the biological sciences. On the one hand it allows an in-depth analysis of the nature and diversity of the conditions under which biological systems display specific behaviors. On the other hand the concept of a disposition may serve a unificatory role in the philosophy of the natural sciences since it captures not only the explanatory practice of biology, but of all natural sciences. Towards the end we will briefly come back to the notion of a potentiality in biology