Search results for "Transient"
showing 10 items of 623 documents
Ancient DNA Reveals Key Stages in the Formation of Central European Mitochondrial Genetic Diversity
2013
The Origins of Europeans To investigate the genetic origins of modern Europeans, Brandt et al. (p. 257 ) examined ancient mitochondrial DNA (mtDNA) and were able to identify genetic differences in 364 Central Europeans spanning the early Neolithic to the Early Bronze Age. Observed changes in mitochondrial haplotypes corresponded with hypothesized human migration across Eurasia and revealed the complexity of the demographic changes and evidence of a Late Neolithic origin for the European mtDNA gene pool. This transect through time reveals four key population events associated with well-known archaeological cultures, which involved genetic influx into Central Europe from various directions at…
Structure of the Human TRPML2 Ion Channel Extracytosolic/Lumenal Domain.
2019
Summary TRPML2 is the least structurally characterized mammalian transient receptor potential mucolipin ion channel. The TRPML family hallmark is a large extracytosolic/lumenal domain (ELD) between transmembrane helices S1 and S2. We present crystal structures of the tetrameric human TRPML2 ELD at pH 6.5 (2.0 A) and 4.5 (2.95 A), corresponding to the pH values in recycling endosomes and lysosomes. Isothermal titration calorimetry shows Ca2+ binding to the highly acidic central pre-pore loop which is abrogated at low pH, in line with a pH-dependent channel regulation model. Small angle X-ray scattering confirms the ELD dimensions in solution. Changes in pH or Ca2+ concentration do not affect…
Molecular and topological membrane folding determinants of transient receptor potential vanilloid 2 channel.
2015
Transient Receptor Potential (TRP) channels are related to adaptation to the environment and somatosensation. The transient receptor potential vanilloid (TRPV) subfamily includes six closely evolutionary related ion channels sharing the same domain organization and tetrameric arrangement in the membrane. In this study we have characterized biochemically TRPV2 channel membrane protein folding and transmembrane (TM) architecture. Deleting the first N-terminal 74 residues preceding the ankyrin repeat domain (ARD) show a key role for this region in targeting the protein to the membrane. We have demonstrated the co-translational insertion of the membrane-embedded region of the TRPV2 and its disp…
The Modular X- and Gamma-Ray Sensor (MXGS)of the ASIM Payload on the International Space Station
2019
The Modular X- and Gamma-ray Sensor (MXGS) is an imaging and spectral X- and Gamma-ray instrument mounted on the starboard side of the Columbus module on the International Space Station. Together with the Modular Multi-Spectral Imaging Assembly (MMIA) (Chanrion et al. this issue) MXGS constitutes the instruments of the Atmosphere-Space Interactions Monitor (ASIM) (Neubert et al. this issue). The main objectives of MXGS are to image and measure the spectrum of X- and γ-rays from lightning discharges, known as Terrestrial Gamma-ray Flashes (TGFs), and for MMIA to image and perform high speed photometry of Transient Luminous Events (TLEs) and lightning discharges. With these two instruments sp…
Cell signaling mechanisms of oro-gustatory detection of dietary fat: Advances and challenges
2013
CD36 and two G-protein coupled receptors (GPCR), i.e., GPR120 and GPR40, have been implicated in the gustatory perception of dietary fats in rodents. These glycoproteins are coupled to increases in free intracellular Ca²⁺ concentrations, [Ca²⁺](i), during their activation by dietary long-chain fatty acids (LCFA). The transient receptor potential type M5 (TRPM5) channel, activated by [Ca²⁺](i), participates in downstream signaling in taste bud cells (TBC). The mice, knocked-out for expression of CD36, GPR120, GPR40 or TRPM5 have a reduced spontaneous preference for fat. The delayed rectifying K⁺ (DRK) channels believed to lie downstream of these receptors are also important players in fat ta…
Drug connectivity mapping and functional analysis reveal therapeutic small molecules that differentially modulate myelination
2022
Disruption or loss of oligodendrocytes (OLs) and myelin has devastating effects on CNS function and integrity, which occur in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular pathways. Here, we have used a combined systems biology and neurobiological approach to identify compounds that exert positive and negative effects on olig…
Implementation of active infrared NDT techniques using long square heating pulses
2012
The present work describes the implementation of active IR Thermography techniques for the NDT of thick polymer and glass-fibre reinforced polymer (GRP) composite panels. A low cost Thermal NDT set-up is proposed, comprising a single-detector IR camera with low thermal resolution and low frame rate, and common low-power halogen lamps as external heat source devices. The use of halogen lamps in particular requires several seconds of switch-on time in order to deliver meaningful and effective heat quantities. The influence of such long heat deposition intervals is investigated on the possibility to implement Transient Thermography and Lock-In Thermography techniques. Regarding the Transient T…
Swings between rotation and accretion power in a binary millisecond pulsar
2013
It is thought that neutron stars in low-mass binary systems can accrete matter and angular momentum from the companion star and be spun-up to millisecond rotational periods1, 2, 3. During the accretion stage, the system is called a low-mass X-ray binary, and bright X-ray emission is observed. When the rate of mass transfer decreases in the later evolutionary stages, these binaries host a radio millisecond pulsar4, 5 whose emission is powered by the neutron star’s rotating magnetic field6. This evolutionary model is supported by the detection of millisecond X-ray pulsations from several accreting neutron stars7, 8 and also by the evidence for a past accretion disc in a rotation-powered milli…
Heptagon-Containing Nanographene Embedded into [10]Cycloparaphenylene
2023
We report the synthesis and characterization of a novel type of nanohoop, consisting of a cycloparaphenylene derivative incorporating a curved heptagon-containing π-extended polycyclic aromatic hydrocarbon (PAH) unit. We demonstrate that this new macrocycle behaves as a supramolecular receptor of curved π-systems such as fullerenes C60 and C70, with remarkably large binding constants (ca. 107 M−1), as estimated by fluorescence measurements. Nanosecond and femtosecond spectroscopic analysis show that these host-guest complexes are capable of quasi-instantaneous charge separation upon photoexcitation, due to the ultrafast charge transfer from the macrocycle to the complexed fullerene. These r…
Redox signaling in acute pancreatitis
2015
Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On th…