661 research outputs found

    Fractal-like structures in colloid science

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    The present work aims at reviewing our current understanding of fractal structures in the frame of colloid aggregation as well as the possibility they offer to produce novel structured materials. In particular, the existing techniques to measure and compute the fractal dimension df are critically discussed based on the cases of organic/inorganic particles and proteins. Then the aggregation conditions affecting df are thoroughly analyzed, pointing out the most recent literature findings and the limitations of our current understanding. Finally, the importance of the fractal dimension in applications is discussed along with possible directions for the production of new structured materials

    The action of physiological and synthetic steroids on the calcium channel CatSper in human sperm

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    The sperm-specific channel CatSper (cation channel of sperm) controls the intracellular Ca2+ concentration ([Ca2+]i) and plays an essential role in sperm function. It is mainly activated by the steroid progesterone (P4) but is also promiscuously activated by a wide range of synthetic and physiological compounds. These compounds include diverse steroids whose action on the channel is so far still controversial. To investigate the effect of these compounds on CatSper and sperm function, we developed a high-throughput screening (HTS) assay to measure changes in [Ca2+]i in human sperm and screened 1,280 approved and off-patent drugs including 90 steroids from the Prestwick chemical library. More than half of the steroids tested (53%) induced an increase in [Ca2+]i and reduced the P4-induced Ca2+ influx in human sperm in a dose-dependent manner. Ten of the most potent steroids (activating and P4-inhibiting) were selected for a detailed analysis of their action on CatSper and their ability to act on sperm acrosome reaction (AR) and penetration in viscous media. We found that these steroids show an inhibitory effect on P4 but not on prostaglandin E1-induced CatSper activation, suggesting that they compete for the same binding site as P4. Pregnenolone, dydrogesterone, epiandrosterone, nandrolone, and dehydroepiandrosterone acetate (DHEA) were found to activate CatSper at physiologically relevant concentrations within the nanomolar range. Like P4, most tested steroids did not significantly affect the AR while stanozolol and estropipate slightly increased sperm penetration into viscous medium. Furthermore, using a hybrid approach integrating pharmacophore analysis and statistical modelling, we were able to screen in silico for steroids that can activate the channel and define the physicochemical and structural properties required for a steroid to exhibit agonist activity against CatSper. Overall, our results indicate that not only physiological but also synthetic steroids can modulate the activity of CatSper with varying potency and if bound to CatSper prior to P4, could impair the timely CatSper activation necessary for proper fertilization to occur

    Medical record: systematic centralization versus secure on demand aggregation

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    <p>Abstract</p> <p>Background</p> <p>As patients often see the data of their medical histories scattered among various medical records hosted in several health-care establishments, the purpose of our multidisciplinary study was to define a pragmatic and secure on-demand based system able to gather this information, with no risk of breaching confidentiality, and to relay it to a medical professional who asked for the information via a specific search engine.</p> <p>Methods</p> <p>Scattered data are often heterogeneous, which makes the task of gathering information very hard. Two methods can be compared: trying to solve the problem by standardizing and centralizing all the information about every patient in a single Medical Record system or trying to use the data "as is" and find a way to obtain the most complete and the most accurate information. Given the failure of the first approach, due to the lack of standardization or privacy and security problems, for example, we propose an alternative that relies on the current state of affairs: an on-demand system, using a specific search engine that is able to retrieve information from the different medical records of a single patient.</p> <p>Results</p> <p>We describe the function of Medical Record Search Engines (MRSE), which are able to retrieve all the available information regarding a patient who has been hospitalized in different hospitals and to provide this information to health professionals upon request. MRSEs use pseudonymized patient identities and thus never have access to the patient's identity. However, though the system would be easy to implement as it by-passes many of the difficulties associated with a centralized architecture, the health professional would have to validate the information, i.e. read all of the information and create his own synthesis and possibly reject extra data, which could be a drawback. We thus propose various feasible improvements, based on the implementation of several tools in our on-demand based system.</p> <p>Conclusions</p> <p>A system that gathers all of the currently available information regarding a patient on the request of health-care professionals could be of great interest. This low-cost pragmatic alternative to centralized medical records could be developed quickly and easily. It could also be designed to include extra features and should thus be considered by health authorities.</p

    Mmf1p, a novel yeast mitochondrial protein conserved throughout evolution and involved in maintenance of the mitochondrial genome

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    A novel protein family (p14.5, or YERO57c/YJGFc) highly conserved throughout evolution has recently been identified. The biological role of these proteins is not yet well characterized. Two members of the p14.5 family are present in the yeast Saccharomyces cerevisiae. In this study, we have characterized some of the biological functions of the two yeast proteins. Mmf1p is a mitochondrial matrix factor, and homologous Mmf1p factor (Hmf1p) copurifies with the soluble cytoplasmic fraction. Δmmf1 cells lose mitochondrial DNA (mtDNA) and have a decreased growth rate, while Δhmf1 cells do not display any visible phenotype. Furthermore, we demonstrate by genetic analysis that Mmf1p does not play a direct role in replication and segregation of the mtDNA. rho(+) Δmmf1 haploid cells can be obtained when tetrads are directly dissected on medium containing a nonfermentable carbon source. Our data also indicate that Mmf1p and Hmf1p have similar biological functions in different subcellular compartments. Hmf1p, when fused with the Mmf1p leader peptide, is transported into mitochondria and is able to functionally replace Mmf1p. Moreover, we show that homologous mammalian proteins are functionally related to Mmf1p. Human p14.5 localizes in yeast mitochondria and rescues the Δmmf1-associated phenotypes. In addition, fractionation of rat liver mitochondria showed that rat p14.5, like Mmf1p, is a soluble protein of the matrix. Our study identifies a biological function for Mmf1p and furthermore indicates that this function is conserved between members of the p14.5 family

    Bmi1 loss produces an increase in astroglial cells and a decrease in neural stem cell population and proliferation

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    The polycomb transcriptional repressor Bmi1 promotes cell cycle progression, controls cell senescence, and is implicated in brain development. Loss of Bmi1 leads to a decreased brain size and causes progressive ataxia and epilepsy. Recently, Bmi1 was shown to control neural stem cell (NSC) renewal. However, the effect of Bmi1 loss on neural cell fate in vivo and the question whether the action of Bmi1 was intrinsic to the NSCs remained to be investigated. Here, we show that Bmi1 is expressed in the germinal zone in vivo and in NSCs as well as in progenitors proliferating in vitro, but not in differentiated cells. Loss of Bmi1 led to a decrease in proliferation in zones known to contain progenitors: the newborn cortex and the newborn and adult subventricular zone. This decrease was accentuated in vitro, where we observed a drastic reduction in NSC proliferation and renewal because of NSC-intrinsic effects of Bmi1 as shown by the means of RNA interference. Bmi1(-/-) mice also presented more astrocytes at birth, and a generalized gliosis at postnatal day 30. At both stages, colocalization of bromodeoxyuridine and GFAP demonstrated that Bmi1 loss did not prevent astrocyte precursor proliferation. Supporting these observations, Bmi1(-/-) neurospheres generate preferentially astrocytes probably attributable to a different responsiveness to environmental factors. Bmi1 is therefore necessary for NSC renewal in a cell-intrinsic mode, whereas the altered cell pattern of the Bmi1(-/-) brain shows that in vivo astrocyte precursors can proliferate in the absence of Bmi1

    First light of the VLT planet finder SPHERE. I. Detection and characterization of the sub-stellar companion GJ 758 B

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    GJ758 B is a brown dwarf companion to a nearby (15.76 pc) solar-type, metal-rich (M/H = +0.2 dex) main-sequence star (G9V) that was discovered with Subaru/HiCIAO in 2009. From previous studies, it has drawn attention as being the coldest (~600K) companion ever directly imaged around a neighboring star. We present new high-contrast data obtained during the commissioning of the SPHERE instrument at the VLT. The data was obtained in Y-, J-, H-, and Ks-bands with the dual-band imaging (DBI) mode of IRDIS, providing a broad coverage of the full near-infrared (near-IR) range at higher contrast and better spectral sampling than previously reported. In this new set of high-quality data, we report the re-detection of the companion, as well as the first detection of a new candidate closer-in to the star. We use the new 8 photometric points for an extended comparison of GJ758 B with empirical objects and 4 families of atmospheric models. From comparison to empirical object, we estimate a T8 spectral type, but none of the comparison object can accurately represent the observed near-IR fluxes of GJ758 B. From comparison to atmospheric models, we attribute a Teff = 600K ±\pm 100K, but we find that no atmospheric model can adequately fit all the fluxes of GJ758 B. The photometry of the new candidate companion is broadly consistent with L-type objects, but a second epoch with improved photometry is necessary to clarify its status. The new astrometry of GJ758 B shows a significant proper motion since the last epoch. We use this result to improve the determination of the orbital characteristics using two fitting approaches, Least-Square Monte Carlo and Markov Chain Monte Carlo. Finally, we analyze the sensitivity of our data to additional closer-in companions and reject the possibility of other massive brown dwarf companions down to 4-5 AU. [abridged]Comment: 20 pages, 15 figures. Accepted for publication in A&
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