Electrostatically gated membrane permeability in inorganic protocells

Although several strategies are now available to produce functional microcompartments analogous to primitive cell-like structures, little progress has been made in generating protocell constructs with self-controlled membrane permeability. Here we describe the preparation of water-dispersible colloidosomes based on silica nanoparticles and delineated by a continuous semipermeable inorganic membrane capable of self-activated, electrostatically gated permeability. We use crosslinking and covalent grafting of a pH-responsive copolymer to generate an ultrathin elastic membrane that exhibits selective release and uptake of small molecules. This behaviour, which depends on the charge of the copolymer coronal layer, serves to trigger enzymatic dephosphorylation reactions specifically within the protocell aqueous interior. This system represents a step towards the design and construction of alternative types of artificial chemical cells and protocell models based on spontaneous processes of inorganic self-organization

Analysis of the backward bending modes in damped rotating beams

[EN] This article presents a study of the backward bending mode of a simply supported rotating Rayleigh beam with internal damping. The study analyses the natural frequency behaviour of the backward mode according to the internal viscous damping ratio, the slenderness of the beam and its spin speed. To date, the behaviour of the natural frequency of the backward mode is known to be a monotonically decreasing function with spin speed due to gyroscopic effects. In this article, however, it is shown that this behaviour of the natural frequency may not hold for certain damping and slenderness conditions, and reaches a minimum value (concave function) from which it begins to increase. Accordingly, the analytical expression of the spin speed for which the natural frequency of the backward mode attains the minimum value has been obtained. In addition, the internal damping ratio and slenderness intervals associated with such behaviour have been also provided.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors gratefully acknowledge the financial support of Ministerio de Ciencia, Innovacion y Universidades Agencia Estatal de Investigacion and the European Regional Development Fund (project TRA2017-84701-R), as well as Generalitat Valenciana (project Prometeo/2016/007) and European Commission through the project 'RUN2Rail - Innovative RUNning gear soluTiOns for new dependable, sustainable, intelligent and comfortable RAIL vehicles' (Horizon 2020 Shift2Rail JU call 2017, grant number 777564)Martínez Casas, J.; Denia Guzmán, FD.; Fayos Sancho, J.; Nadal, E.; Giner Navarro, J. (2019). Analysis of the backward bending modes in damped rotating beams. Advances in Mechanical Engineering. 11(4):1-13. https://doi.org/10.1177/1687814019840474S113114Zorzi, E. S., & Nelson, H. D. (1977). Finite Element Simulation of Rotor-Bearing Systems With Internal Damping. Journal of Engineering for Power, 99(1), 71-76. doi:10.1115/1.3446254Ku, D.-M. (1998). FINITE ELEMENT ANALYSIS OF WHIRL SPEEDS FOR ROTOR-BEARING SYSTEMS WITH INTERNAL DAMPING. Mechanical Systems and Signal Processing, 12(5), 599-610. doi:10.1006/mssp.1998.0159Dimentberg, M. F. (2005). Vibration of a rotating shaft with randomly varying internal damping. Journal of Sound and Vibration, 285(3), 759-765. doi:10.1016/j.jsv.2004.11.025Vatta, F., & Vigliani, A. (2008). Internal damping in rotating shafts. Mechanism and Machine Theory, 43(11), 1376-1384. doi:10.1016/j.mechmachtheory.2007.12.009Rosales, M. B., & Filipich, C. P. (1993). Dynamic Stability of a Spinning Beam Carrying an Axial Dead Load. Journal of Sound and Vibration, 163(2), 283-294. doi:10.1006/jsvi.1993.1165Mazzei, A. J., & Scott, R. A. (2003). Effects of internal viscous damping on the stability of a rotating shaft driven through a universal joint. Journal of Sound and Vibration, 265(4), 863-885. doi:10.1016/s0022-460x(02)01256-7Ehrich, F. F. (1964). Shaft Whirl Induced by Rotor Internal Damping. Journal of Applied Mechanics, 31(2), 279-282. doi:10.1115/1.3629598Vance, J. M., & Lee, J. (1974). Stability of High Speed Rotors With Internal Friction. Journal of Engineering for Industry, 96(3), 960-968. doi:10.1115/1.3438468Vila, P., Baeza, L., Martínez-Casas, J., & Carballeira, J. (2014). Rail corrugation growth accounting for the flexibility and rotation of the wheel set and the non-Hertzian and non-steady-state effects at contact patch. Vehicle System Dynamics, 52(sup1), 92-108. doi:10.1080/00423114.2014.881513Glocker, C., Cataldi-Spinola, E., & Leine, R. I. (2009). Curve squealing of trains: Measurement, modelling and simulation. Journal of Sound and Vibration, 324(1-2), 365-386. doi:10.1016/j.jsv.2009.01.048Bauer, H. F. (1980). Vibration of a rotating uniform beam, part I: Orientation in the axis of rotation. Journal of Sound and Vibration, 72(2), 177-189. doi:10.1016/0022-460x(80)90651-3Shiau, T. N., & Hwang, J. L. (1993). Generalized Polynomial Expansion Method for the Dynamic Analysis of Rotor-Bearing Systems. Journal of Engineering for Gas Turbines and Power, 115(2), 209-217. doi:10.1115/1.2906696Hili, M. A., Fakhfakh, T., & Haddar, M. (2006). Vibration analysis of a rotating flexible shaft–disk system. Journal of Engineering Mathematics, 57(4), 351-363. doi:10.1007/s10665-006-9060-3Young, T. H., Shiau, T. N., & Kuo, Z. H. (2007). Dynamic stability of rotor-bearing systems subjected to random axial forces. Journal of Sound and Vibration, 305(3), 467-480. doi:10.1016/j.jsv.2007.04.016Wang, J., Hurskainen, V.-V., Matikainen, M. K., Sopanen, J., & Mikkola, A. (2017). On the dynamic analysis of rotating shafts using nonlinear superelement and absolute nodal coordinate formulations. Advances in Mechanical Engineering, 9(11), 168781401773267. doi:10.1177/1687814017732672Lee, C.-W. (1993). Vibration Analysis of Rotors. Solid Mechanics and Its Applications. doi:10.1007/978-94-015-8173-8Genta, G. (1999). Vibration of Structures and Machines. doi:10.1007/978-1-4612-1450-2Cheng, C. C., & Lin, J. K. (2003). Modelling a rotating shaft subjected to a high-speed moving force. Journal of Sound and Vibration, 261(5), 955-965. doi:10.1016/s0022-460x(02)01374-

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Childhood leukemia: electric and magnetic fields as possible risk factors.

Numerous epidemiologic studies have reported associations between measures of power-line electric or magnetic fields (EMFs) and childhood leukemia. The basis for such associations remains unexplained. In children, acute lymphoblastic leukemia represents approximately three-quarters of all U.S. leukemia types. Some risk factors for childhood leukemia have been established, and others are suspected. Pathogenesis, as investigated in animal models, is consistent with the multistep model of acute leukemia development. Studies of carcinogenicity in animals, however, are overwhelmingly negative and do not support the hypothesis that EMF exposure is a significant risk factor for hematopoietic neoplasia. We may fail to observe effects from EMFs because, from a mechanistic perspective, the effects of EMFs on biology are very weak. Cells and organs function despite many sources of chemical "noise" (e.g., stochastic, temperature, concentration, mechanical, and electrical noise), which exceed the induced EMF "signal" by a large factor. However, the inability to detect EMF effects in bioassay systems may be caused by the choice made for "EMF exposure." "Contact currents" or "contact voltages" have been proposed as a novel exposure metric, because their magnitude is related to measured power-line magnetic fields. A contact current occurs when a person touches two conductive surfaces at different voltages. Modeled analyses support contact currents as a plausible metric because of correlations with residential magnetic fields and opportunity for exposure. The possible role of contact currents as an explanatory variable in the reported associations between EMFs and childhood leukemia will need to be clarified by further measurements, biophysical analyses, bioassay studies, and epidemiology

Expression profiles of hydrophobic surfactant proteins in children with diffuse chronic lung disease

BACKGROUND: Abnormalities of the intracellular metabolism of the hydrophobic surfactant proteins SP-B and SP-C and their precursors may be causally linked to chronic childhood diffuse lung diseases. The profile of these proteins in the alveolar space is unknown in such subjects. METHODS: We analyzed bronchoalveolar lavage fluid by Western blotting for SP-B, SP-C and their proforms in children with pulmonary alveolar proteinosis (PAP, n = 15), children with no SP-B (n = 6), children with chronic respiratory distress of unknown cause (cRD, n = 7), in comparison to children without lung disease (n = 15) or chronic obstructive bronchitis (n = 19). RESULTS: Pro-SP-B of 25–26 kD was commonly abundant in all groups of subjects, suggesting that their presence is not of diagnostic value for processing defects. In contrast, pro-SP-B peptides cleaved off during intracellular processing of SP-B and smaller than 19–21 kD, were exclusively found in PAP and cRD. In 4 of 6 children with no SP-B, mutations of SFTPB or SPTPC genes were found. Pro-SP-C forms were identified at very low frequency. Their presence was clearly, but not exclusively associated with mutations of the SFTPB and SPTPC genes, impeding their usage as candidates for diagnostic screening. CONCLUSION: Immuno-analysis of the hydrophobic surfactant proteins and their precursor forms in bronchoalveolar lavage is minimally invasive and can give valuable clues for the involvement of processing abnormalities in pediatric pulmonary disorders

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

Is Lamarckian evolution relevant to medicine?

BACKGROUND: 200 years have now passed since Darwin was born and scientists around the world are celebrating this important anniversary of the birth of an evolutionary visionary. However, the theories of his colleague Lamarck are treated with considerably less acclaim. These theories centre on the tendency for complexity to increase in organisms over time and the direct transmission of phenotypic traits from parents to offspring. DISCUSSION: Lamarckian concepts, long thought of no relevance to modern evolutionary theory, are enjoying a quiet resurgence with the increasing complexity of epigenetic theories of inheritance. There is evidence that epigenetic alterations, including DNA methylation and histone modifications, are transmitted transgenerationally, thus providing a potential mechanism for environmental influences to be passed from parents to offspring: Lamarckian evolution. Furthermore, evidence is accumulating that epigenetics plays an important role in many common medical conditions. SUMMARY: Epigenetics allows the peaceful co-existence of Darwinian and Lamarckian evolution. Further efforts should be exerted on studying the mechanisms by which this occurs so that public health measures can be undertaken to reverse or prevent epigenetic changes important in disease susceptibility. Perhaps in 2059 we will be celebrating the anniversary of both Darwin and Lamarck

Recombination in West Nile Virus: minimal contribution to genomic diversity

Recombination is known to play a role in the ability of various viruses to acquire sequence diversity. We consequently examined all available West Nile virus (WNV) whole genome sequences both phylogenetically and with a variety of computational recombination detection algorithms. We found that the number of distinct lineages present on a phylogenetic tree reconstruction to be identical to the 6 previously reported. Statistically-significant evidence for recombination was only observed in one whole genome sequence. This recombination event was within the NS5 polymerase coding region. All three viruses contributing to the recombination event were originally isolated in Africa at various times, with the major parent (SPU116_89_B), minor parent (KN3829), and recombinant sequence (AnMg798) belonging to WNV taxonomic lineages 2, 1a, and 2 respectively. This one isolated recombinant genome was out of a total of 154 sequences analyzed. It therefore does not seem likely that recombination contributes in any significant manner to the overall sequence variation within the WNV genome

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

4-Phenylbutyric acid treatment rescues trafficking and processing of a mutant surfactant protein C

Mutations in the SFTPC gene, encoding surfactant protein–C (SP-C), are associated with interstitial lung disease (ILD). Knowledge of the intracellular fate of mutant SP-C is essential in the design of therapies to correct trafficking/processing of the proprotein, and to prevent the formation of cytotoxic aggregates. We assessed the potential of a chemical chaperone to correct the trafficking and processing of three disease-associated mutant SP-C proteins. HEK293 cells were stably transfected with wild-type (SP-C(WT)) or mutant (SP-C(L188Q), SP-C(Δexon4), or SP-C(I73T)) SP-C, and cell lines with a similar expression of SP-C mRNA were identified. The effects of the chemical chaperone 4-phenylbutyric acid (PBA) and lysosomotropic drugs on intracellular trafficking to the endolysosomal pathway and the subsequent conversion of SP-C proprotein to mature peptide were assessed. Despite comparable SP-C mRNA expression, proprotein concentrations varied greatly: SP-C(I73T) was more abundant than SP-C(WT) and was localized to the cell surface, whereas SP-C(Δexon4) was barely detectable. In contrast, SP-C(L188Q) and SP-C(WT) proprotein concentrations were comparable, and a small amount of SP-C(L188Q) was localized to the endolysosomal pathway. PBA treatment restored the trafficking and processing of SP-C(L188Q) to SP-C(WT) concentrations, but did not correct the mistrafficking of SP-C(I73T) or rescue SP-C(Δexon4). PBA treatment also promoted the aggregation of SP-C proproteins, including SP-C(L188Q). This study provides proof of the principle that a chemical chaperone can correct the mistrafficking and processing of a disease-associated mutant SP-C proprotein