In-tissue embedded magnetic nanoparticle (MNPs) detection is one of the most interesting cases for cancer research. In order to understand the origin, the limits and the way of improvement of ...magnetic biosensor sensitivity for the detection of 3D mezoscopic distributions of MNPs, we have developed a magnetoimpedance biosensor prototype with a Cu (3 nm)/FeNi(100 nm)5/Cu(500 nm)/FeNi(100 nm)/Cu(3 nm)5 rectangular sensitive element. Magnetoimpedance (MI) responses were measured with and without polyacrylamide ferrogel layer mimicking natural tissue in order to evaluate stray fields of embedded MNPs of γ-Fe2O3 iron oxide. A model for MI response based on a solution of Maxwell equations with Landau-Lifshitz equation was developed in order to understand the origin of the prototype sensitivity which reached 1.3% of ΔZ/Z per 1% of MNPs concentration by weight. To make this promising technique useful for magnetically labeled tissue detection, a synthesis of composite gels with MNPs agglomerates compactly located inside pure gel and their MI testing are still necessary.
•Magnetoimpedance (MI) biosensor prototype with Cu/FeNi5/Cu/FeNi/Cu5 element was designed and tested.•MI responses were measured with and without ferrogel layer mimicking natural tissue.•We were able to evaluate stray fields of 3D distributions of embedded magnetic nanoparticles.•Electromagnetic MI model was developed in order to understand the 1.3% of ΔZ/Z per 1 wt% of MNPs concentration prototype sensitivity.
The most superficial layer of the spinal dorsal horn, lamina I, is a key element of the nociceptive processing system. It contains different types of projection neurons (PNs) and local-circuit ...neurons (LCNs) whose functional roles in the signal processing are poorly understood. This article reviews recent progress in elucidating novel anatomical features and physiological properties of lamina I PNs and LCNs revealed by whole-cell recordings in ex vivo spinal cord.
This article is part of the Special Issue on “Ukrainian Neuroscience”.
•Recording in ex vivo spinal cord reveals novel properties of lamina I neurons.•Most projection neurons have different types of local axon collaterals.•GABAergic local-circuit neurons in lamina I show intrinsic rhythmic firing.•Lamina I neurons integrate broad input from Aβ-, Aδ- and C-afferent fibers.•Lamina I is involved in somatovisceral, trigeminocervical and bilateral integration.
ABSTRACT
The existence of high-energy astrophysical neutrinos has been unambiguously demonstrated, but their sources remain elusive. IceCube reported an association of a 290-TeV neutrino with a ...gamma-ray flare of TXS 0506 + 056, an active galactic nucleus with a compact radio jet pointing to us. Later, radio-bright blazars were shown to be associated with IceCube neutrino events with high statistical significance. These associations remained unconfirmed with the data of independent experiments. Here, we report on the detection of a rare neutrino event with the estimated energy of 224 ± 75 TeV from the direction of TXS 0506 + 056 by the new Baikal Gigaton Volume Detector (Baikal-GVD) in April 2021. This event is the highest energy cascade detected so far by the Baikal-GVD neutrino telescope from a direction below horizon. The result supports previous suggestions that radio blazars in general, and TXS 0506 + 056 in particular, are the sources of high-energy neutrinos, and opens up the cascade channel for the neutrino astronomy.
The importance of 3D protein structure in proteolytic processing is well known. However, despite the plethora of existing methods for predicting proteolytic sites, only a few of them utilize the ...structural features of potential substrates as predictors. Moreover, to our knowledge, there is currently no method available for predicting the structural susceptibility of protein regions to proteolysis. We developed such a method using data from CutDB, a database that contains experimentally verified proteolytic events. For prediction, we utilized structural features that have been shown to influence proteolysis in earlier studies, such as solvent accessibility, secondary structure, and temperature factor. Additionally, we introduced new structural features, including length of protruded loops and flexibility of protein termini. To maximize the prediction quality of the method, we carefully curated the training set, selected an appropriate machine learning method, and sampled negative examples to determine the optimal positive-to-negative class size ratio. We demonstrated that combining our method with models of protease primary specificity can outperform existing bioinformatics methods for the prediction of proteolytic sites. We also discussed the possibility of utilizing this method for bioinformatics prediction of other post-translational modifications.
The Advanced Laser Interferometer Gravitational-Wave Observatory and Advanced Virgo observatories recently discovered gravitational waves from a binary neutron star inspiral. A short gamma-ray burst ...that followed the merger of this binary was also recorded by Fermi gamma-ray burst monitor and International Gamma-Ray Astrophysics Laboratory, indicating particle acceleration by the source. The precise location of the event was determined by optical detections of emission following the merger. We searched for high-energy neutrinos from the merger in the energy range of 1 TeV–100 PeV using the Baikal Gigaton Volume Detector. No neutrinos directionally coincident with the source were detected within ±500 s around the merger time, as well as during a 14-day period after the gravitational wave detection. We derived 90% C.L. upper limits on the neutrino fluence from GW170817 during a ±500 s window centered on the gravitational wave trigger time, and a 14-day window following the gravitational wave signal under the assumption of an
E
−2
neutrino energy spectrum.
Hydrogels are biomimetic materials widely used in the area of biomedical engineering and biosensing. Ferrogels (FG) are magnetic composites capable of functioning as magnetic field sensitive ...transformers and field assisted drug deliverers. FG can be prepared by incorporating magnetic nanoparticles (MNPs) into chemically crosslinked hydrogels. The properties of biomimetic ferrogels for multifunctional biosensor applications can be set up by synthesis. The properties of these biomimetic ferrogels can be thoroughly controlled in a physical experiment environment which is much less demanding than biotests. Two series of ferrogels (soft and dense) based on polyacrylamide (PAAm) with different chemical network densities were synthesized by free-radical polymerization in aqueous solution with
,
'-methylene-diacrylamide as a cross-linker and maghemite Fe₂O₃ MNPs fabricated by laser target evaporation as a filler. Their mechanical, electrical and magnetic properties were comparatively analyzed. We developed a giant magnetoimpedance (MI) sensor prototype with multilayered FeNi-based sensitive elements deposited onto glass or polymer substrates adapted for FG studies. The MI measurements in the initial state and in the presence of FG with different concentrations of MNPs at a frequency range of 1-300 MHz allowed a precise characterization of the stray fields of the MNPs present in the FG. We proposed an electrodynamic model to describe the MI in multilayered film with a FG layer based on the solution of linearized Maxwell equations for the electromagnetic fields coupled with the Landau-Lifshitz equation for the magnetization dynamics.
Thermal activation of transient receptor potential (TRP) cation channels is one of the most striking examples of temperature-controlled processes in cell biology. As the evidence indicating the ...fundamental role of such processes in thermosensation builds at a fast pace, adequately accurate tools that would allow heat receptor logic behind thermosensation to be examined on a single-cell level are in great demand. Here, we demonstrate a specifically designed fiber-optic probe that enables thermal activation with simultaneous online thermometry of individual cells expressing genetically encoded TRP channels. This probe integrates a fiber-optic tract for the delivery of laser light with a two-wire microwave transmission line. A diamond microcrystal fixed on the fiber tip is heated by laser radiation transmitted through the fiber, providing a local heating of a cell culture, enabling a well-controlled TRP-assisted thermal activation of cells. Online local temperature measurements are performed by using the temperature-dependent frequency shift of optically detected magnetic resonance, induced by coupling the microwave field, delivered by the microwave transmission line, to nitrogen--vacancy centers in the diamond microcrystal. Activation of TRP channels is verified by using genetically encoded fluorescence indicators, visualizing an increase in the calcium flow through activated TRP channels.
Mitochondrial localization of SESN2 Kovaleva, Irina E; Tokarchuk, Artem V; Zheltukhin, Andrei O ...
PloS one,
04/2020, Letnik:
15, Številka:
4
Journal Article
Recenzirano
Odprti dostop
SESN2 is a member of the evolutionarily conserved sestrin protein family found in most of the Metazoa species. The SESN2 gene is transcriptionally activated by many stress factors, including ...metabolic derangements, reactive oxygen species (ROS), and DNA-damage. As a result, SESN2 controls ROS accumulation, metabolism, and cell viability. The best-known function of SESN2 is the inhibition of the mechanistic target of rapamycin complex 1 kinase (mTORC1) that plays a central role in support of cell growth and suppression of autophagy. SESN2 inhibits mTORC1 activity through interaction with the GATOR2 protein complex preventing an inhibitory effect of GATOR2 on the GATOR1 protein complex. GATOR1 stimulates GTPase activity of the RagA/B small GTPase, the component of RagA/B:RagC/D complex, preventing mTORC1 translocation to the lysosomes and its activation by the small GTPase Rheb. Despite the well-established role of SESN2 in mTORC1 inhibition, other SESN2 activities are not well-characterized. We recently showed that SESN2 could control mitochondrial function and cell death via mTORC1-independent mechanisms, and these activities might be explained by direct effects of SESN2 on mitochondria. In this work, we examined mitochondrial localization of SESN2 and demonstrated that SESN2 is located on mitochondria and can be directly involved in the regulation of mitochondrial functions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Neurons devoid of plasmalogens have impaired excitability.•Plasmalogen deficiency causes a distal repositioning of the axon initial segment (AIS).•Identification of the AKT-ULK1 ...signaling cascade as regulator of AIS positioning•Rescuing plasmalogens or the defective signaling pathway restores normal AIS localization.
The axon initial segment (AIS) is a specialized region in neurons that encompasses two essential functions, the generation of action potentials and the regulation of the axodendritic polarity. The mechanism controlling the position of the axon initial segment to allow plasticity and regulation of neuron excitability is unclear. Here we demonstrate that plasmalogens, the most abundant ether-phospholipid, are essential for the homeostatic positioning of the AIS. Plasmalogen deficiency is a hallmark of Rhizomelic Chondrodysplasia Punctata (RCDP) and Zellweger spectrum disorders, but Alzheimer’s and Parkinson’s disease, are also characterized by plasmalogen defects. Neurons lacking plasmalogens displaced the AIS to more distal positions and were characterized by reduced excitability. Treatment with a short-chain alkyl glycerol was able to rescue AIS positioning. Plasmalogen deficiency impaired AKT activation, and we show that inhibition of AKT phosphorylation at Ser473 and Thr308 is sufficient to induce a distal relocation of the AIS. Pathway analysis revealed that downstream of AKT, overtly active ULK1 mediates AIS repositioning. Rescuing the impaired AKT signaling pathway was able to normalize AIS position independently of the biochemical defect. These results unveil a previously unknown mechanism that couples the phospholipid composition of the neuronal membrane to the positional assembly of the AIS.
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