168 research outputs found
Extreme accumulation of nucleotides in simulated hydrothermal pore systems
We simulate molecular transport in elongated hydrothermal pore systems influenced by a thermal gradient. We find extreme accumulation of molecules in a wide variety of plugged pores. The mechanism is able to provide highly concentrated single nucleotides, suitable for operations of an RNA world at the origin of life. It is driven solely by the thermal gradient across a pore. On the one hand, the fluid is shuttled by thermal convection along the pore, whereas on the other hand, the molecules drift across the pore, driven by thermodiffusion. As a result, millimeter-sized pores accumulate even single nucleotides more than 108-fold into micrometer-sized regions. The enhanced concentration of molecules is found in the bulk water near the closed bottom end of the pore. Because the accumulation depends exponentially on the pore length and temperature difference, it is considerably robust with respect to changes in the cleft geometry and the molecular dimensions. Whereas thin pores can concentrate only long polynucleotides, thicker pores accumulate short and long polynucleotides equally well and allow various molecular compositions. This setting also provides a temperature oscillation, shown previously to exponentially replicate DNA in the protein-assisted PCR. Our results indicate that, for life to evolve, complicated active membrane transport is not required for the initial steps. We find that interlinked mineral pores in a thermal gradient provide a compelling high-concentration starting point for the molecular evolution of life
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Real-time monitoring of cell surface protein arrival with split luciferases
Each cell in a multicellular organism permanently adjusts the concentration of its cell surface proteins. In particular, epithelial cells tightly control the number of carriers, transporters and cell adhesion proteins at their plasma membrane. However, sensitively measuring the cell surface concentration of a particular protein of interest in live cells and in real time represents a considerable challenge. Here, we introduce a novel approach based on split luciferases, which uses one luciferase fragment as a tag on the protein of interest and the second fragment as a supplement to the extracellular medium. Once the protein of interest arrives at the cell surface, the luciferase fragments complement and generate luminescence. We compared the performance of split Gaussia luciferase and split Nanoluciferase by using a system to synchronize biosynthetic trafficking with conditional aggregation domains. The best results were achieved with split Nanoluciferase, for which luminescence increased more than 6000-fold upon recombination. Furthermore, we showed that our approach can separately detect and quantify the arrival of membrane proteins at the apical and basolateral plasma membrane in single polarized epithelial cells by detecting the luminescence signals with a microscope, thus opening novel avenues for characterizing the variations in trafficking in individual epithelial cells
Sub-kHz lasing of a CaF_2 Whispering Gallery Mode Resonator Stabilized Fiber Ring Laser
We utilize a high quality calcium fluoride whispering-gallery-mode resonator
to stabilize a simple erbium doped fiber ring laser with an emission frequency
of 196 THz (wavelenght 1530 nm) to a linewidth below 650 Hz. This corresponds
to a relative stability of 3.3 x 10^(-12) over 16 \mus. In order to
characterize the linewidth we use two identical self-built lasers and a
commercial laser to determine the individual lasing linewidth via the
three-cornered hat method.Comment: 4 pages, 3 figure
The origin of life: chemical evolution of a metabolic system in a mineral honeycomb?
For the RNA-world hypothesis to be ecologically feasible, selection mechanisms acting on replicator communities need to be invoked and the corresponding scenarios of molecular evolution specified. Complementing our previous models of chemical evolution on mineral surfaces, in which selection was the consequence of the limited mobility of macromolecules attached to the surface, here we offer an alternative realization of prebiotic group-level selection: the physical encapsulation of local replicator communities into the pores of the mineral substrate. Based on cellular automaton simulations we argue that the effect of group selection in a mineral honeycomb could have been efficient enough to keep prebiotic ribozymes of different specificities and replication rates coexistent, and their metabolic cooperation protected from extensive molecular parasitism. We suggest that mutants of the mild parasites persistent in the metabolic system can acquire useful functions such as replicase activity or the production of membrane components, thus opening the way for the evolution of the first autonomous protocells on Earth
Exposure Setup and Dosimetry for a Study on Effects of Mobile Communication Signals on Human Hematopoietic Stem Cells in vitro
In this paper we describe the design of an exposure setup used to
study possible non-thermal effects due to the exposure of human hematopoietic
stem cells to GSM, UMTS and LTE mobile communication signals. The experiments
are performed under fully blinded conditions in a TEM waveguide located
inside an incubator to achieve defined environmental conditions as required
for the living cells. Chamber slides containing the cells in culture medium
are placed on the septum of the waveguide. The environmental and exposure
parameters such as signal power, temperatures, relative humidity and CO2
content of the surrounding atmosphere are monitored permanently during the
exposure experiment. The power of the exposure signals required to achieve
specific absorption rates of 0.5, 1, 2 and 4 W kg−1 are
determined by numerical calculation of the field distribution inside the cell
culture medium at 900 MHz (GSM), 1950 MHz (UMTS) and 2535 MHz (LTE). The
dosimetry is verified both with scattering parameter measurements on the
waveguide with and without containers filled with cell culture medium and
with temperature measurements with non-metallic probes in separate heating
experiments
Structure and function analyses of the purified GPCR human vomeronasal type 1 receptor 1
The vomeronasal system is one of several fine-tuned scent-detecting signaling systems in
mammals. However, despite significant efforts, how these receptors detect scent remains an
enigma. One reason is the lack of sufficient purified receptors to perform detailed
biochemical, biophysical and structural analyses. Here we report the ability to express and
purify milligrams of purified, functional human vomeronasal receptor hVN1R1. Circular
dichroism showed that purified hVN1R1 had an alpha-helical structure, similar to that of
other GPCRs. Microscale thermophoresis showed that hVN1R1 bound its known ligand myrtenal
with an EC50 ∼1 µM. This expression system can enable structural and functional
analyses towards understanding how mammalian scent detection works
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
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
Phase-Dependent Suppression of Beta Oscillations in Parkinson's Disease Patients
Synchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (∼20 Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson's disease patients. Computational modeling suggests that the amplitude of such oscillations could be modulated by applying stimulation at a specific phase. Such a strategy would allow selective targeting of the oscillation, with relatively little effect on other activity parameters. Here, activity was recorded from 10 awake, parkinsonian patients (6 male, 4 female human subjects) undergoing functional neurosurgery. We demonstrate that stimulation arriving on a particular patient-specific phase of the beta oscillation over consecutive cycles could suppress the amplitude of this pathophysiological activity by up to 40%, while amplification effects were relatively weak. Suppressive effects were accompanied by a reduction in the rhythmic output of subthalamic nucleus (STN) neurons and synchronization with the mesial cortex. While stimulation could alter the spiking pattern of STN neurons, there was no net effect on firing rate, suggesting that reduced beta synchrony was a result of alterations to the relative timing of spiking activity, rather than an overall change in excitability. Together, these results identify a novel intrinsic property of cortico-basal ganglia synchrony that suggests the phase of ongoing neural oscillations could be a viable and effective control signal for the treatment of Parkinson's disease. This work has potential implications for other brain diseases with exaggerated neuronal synchronization and for probing the function of rhythmic activity in the healthy brain
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