V první části článku autor podrobně klasifikuje biosignaly z nejrůznějších hledisek Výsledky uvádí v přebiednych tabulkách pro nativní biosignály. Konkrétní příklady jsou zvoleny z růzjtých klinických oborů s cílem ukázat použití biosignálů v současné medicíně a v příbuzných oborech.
In the article the biosignals in detail are classified from various sides of view. The results for native biosignals are presented in lucid tables. The concrete examples are chosen from various clinical branches with goal of showing use of biosignals in present medicine.
The stringent response enables bacteria to respond to nutrient limitation and other stress conditions through production of the nucleotide-based second messengers ppGpp and pppGpp, collectively known as (p)ppGpp. Here, we report that (p)ppGpp inhibits the signal recognition particle (SRP)-dependent protein targeting pathway, which is essential for membrane protein biogenesis and protein secretion. More specifically, (p)ppGpp binds to the SRP GTPases Ffh and FtsY, and inhibits the formation of the SRP receptor-targeting complex, which is central for the coordinated binding of the translating ribosome to the SecYEG translocon. Cryo-EM analysis of SRP bound to translating ribosomes suggests that (p)ppGpp may induce a distinct conformational stabilization of the NG domain of Ffh and FtsY in Bacillus subtilis but not in E. coli.
- MeSH
- Bacterial Proteins metabolism MeSH
- Escherichia coli metabolism MeSH
- Guanosine Pentaphosphate metabolism MeSH
- Escherichia coli Proteins * metabolism MeSH
- Receptors, Cytoplasmic and Nuclear metabolism MeSH
- Signal Recognition Particle * metabolism MeSH
- Protein Binding MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Killer Cells, Natural cytology physiology MeSH
- Genetic Engineering trends MeSH
- Humans MeSH
- Cell Adhesion Molecules physiology chemistry metabolism MeSH
- Receptors, Cell Surface physiology chemistry metabolism MeSH
- Receptors, Leukocyte-Adhesion metabolism MeSH
- Signal Recognition Particle genetics metabolism MeSH
- Signal Transduction MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Review MeSH
Hyperintenzity v bílé hmotě mozkové v T2 váženém obraze jsou velmi senzitivní, ale obecně jen málo specifickou charakteristikou řady neurologických onemocnění. K určení substrátové diagnózy těchto ložisek je nezbytná znalost dostupných klinických údajů spolu s výsledky paraklinických testů. Přesto při vzájemné korelaci obvykle užívaných sekvencí T1W(SE), T2W(TSE), FLAIR a PD(TSE), popřípadě aplikací Gd-DTPA v modu T1W SE, můžeme v řadě případů již z distribuce a charakteru signálu v obraze magnetické rezonance vyslovit s větší či menší pravděpodobností určité podezření na substrátovou diagnózu nebo alespoň zúžit možnosti diferenciální diagnostiky.
White matter hyperintensities on T2 weighted images are a sensitive but in general non-specific characteristic of many diseases of the CNS. For diagnosis of these lesions it is necessary to collect all the clinical data available including results of other auxiliary paraclinical tests. Despite these facts correlation of the most frequently used sequences: Tl weighted Spin Echo, T2 weighted Turbo Spin Echo, proton density Turbo Spin Echo, FLAIR (Fluid Attenuated Inversion Recovery) and Gd-enhanced Tl weighted Spin Echo may either decide the diagnosis or at least make our differential diagnostic considerations more accurate.
- MeSH
- Diagnosis, Differential MeSH
- Research Support as Topic MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain Diseases MeSH
- Signal Recognition Particle MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Comparative Study MeSH
- Keywords
- antisyntetázový syndrom,
- MeSH
- Autoantibodies physiology adverse effects MeSH
- Hydroxymethylglutaryl CoA Reductases immunology MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Humans MeSH
- Myositis * diagnosis etiology drug therapy chemically induced classification MeSH
- Necrosis diagnosis etiology pathology MeSH
- Muscular Diseases * diagnosis etiology drug therapy chemically induced classification MeSH
- Signal Recognition Particle immunology MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors * adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The mechanism of action of various viruses has been the primary focus of many studies. Yet, the data on RNA modifications in any type of virus are scarce. Methods for the sensitive analysis of RNA modifications have been developed only recently and they have not been applied to viruses. In particular, the RNA composition of HIV-1 virions has never been determined with sufficiently exact methods. Here, we reveal that the RNA of HIV-1 virions contains surprisingly high amount of the 1-methyladenosine. We are the first to use a liquid chromatography-mass spectrometry analysis (LC/MS) of virion RNA, which we combined with m1A profiling and deep sequencing. We found that m1A was present in the tRNA, but not in the genomic HIV-1 RNA and the abundant 7SL RNA. We were able to calculate that an HIV-1 virion contains per 2 copies of genomic RNA and 14 copies of 7SL RNA also 770 copies of tRNA, which is approximately 10 times more than thus far expected. These new insights into the composition of the HIV-1 virion can help in future studies to identify the role of nonprimer tRNAs in retroviruses. Moreover, we present a promising new tool for studying the compositions of virions.
- MeSH
- Adenosine analogs & derivatives metabolism MeSH
- Chromatography, Liquid methods MeSH
- Genome, Viral genetics MeSH
- HIV-1 genetics physiology MeSH
- Mass Spectrometry methods MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- RNA, Small Cytoplasmic genetics MeSH
- RNA, Transfer genetics metabolism MeSH
- RNA, Viral genetics metabolism MeSH
- Base Sequence MeSH
- Virus Assembly genetics MeSH
- Signal Recognition Particle genetics MeSH
- Virion genetics metabolism MeSH
- High-Throughput Nucleotide Sequencing methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The metazoan Sec61 translocon transports polypeptides into and across the membrane of the endoplasmic reticulum via two major routes, a well-established co-translational pathway and a post-translational alternative. We have used two model substrates to explore the elements of a secretory protein precursor that preferentially direct it towards a co- or post-translational pathway for ER translocation. Having first determined the capacity of precursors to enter ER derived microsomes post-translationally, we then exploited semi-permeabilized mammalian cells specifically depleted of key membrane components using siRNA to address their contribution to the membrane translocation process. These studies suggest precursor chain length is a key factor in the post-translational translocation at the mammalian ER, and identify Sec62 and Sec63 as important components acting on this route. This role for Sec62 and Sec63 is independent of the signal sequence that delivers the precursor to the ER. However, the signal sequence can influence the subsequent membrane translocation process, conferring sensitivity to a small molecule inhibitor and dictating reliance on the molecular chaperone BiP. Our data support a model where secretory protein precursors that fail to engage the signal recognition particle, for example because they are short, are delivered to the ER membrane via a distinct route that is dependent upon both Sec62 and Sec63. Although this requirement for Sec62 and Sec63 is unaffected by the specific signal sequence that delivers a precursor to the ER, this region can influence subsequent events, including both Sec61 mediated transport and the importance of BiP for membrane translocation. Taken together, our data suggest that an ER signal sequence can regulate specific aspects of Sec61 mediated membrane translocation at a stage following Sec62/Sec63 dependent ER delivery.
Objective.This work presents a method for enhanced detection, imaging, and measurement of the thermal neutron flux.Approach. Measurements were performed in a water tank, while the detector is positioned out-of-field of a 20 MeV ultra-high pulse dose rate electron beam. A semiconductor pixel detector Timepix3 with a silicon sensor partially covered by a6LiF neutron converter was used to measure the flux, spatial, and time characteristics of the neutron field. To provide absolute measurements of thermal neutron flux, the detection efficiency calibration of the detectors was performed in a reference thermal neutron field. Neutron signals are recognized and discriminated against other particles such as gamma rays and x-rays. This is achieved by the resolving power of the pixel detector using machine learning algorithms and high-resolution pattern recognition analysis of the high-energy tracks created by thermal neutron interactions in the converter.Main results. The resulting thermal neutrons equivalent dose was obtained using conversion factor (2.13(10) pSv·cm2) from thermal neutron fluence to thermal neutron equivalent dose obtained by Monte Carlo simulations. The calibrated detectors were used to characterize scattered radiation created by electron beams. The results at 12.0 cm depth in the beam axis inside of the water for a delivered dose per pulse of 1.85 Gy (pulse length of 2.4μs) at the reference depth, showed a contribution of flux of 4.07(8) × 103particles·cm-2·s-1and equivalent dose of 1.73(3) nSv per pulse, which is lower by ∼9 orders of magnitude than the delivered dose.Significance. The presented methodology for in-water measurements and identification of characteristic thermal neutrons tracks serves for the selective quantification of equivalent dose made by thermal neutrons in out-of-field particle therapy.
- MeSH
- Algorithms * MeSH
- Electrons * MeSH
- Calibration MeSH
- Neutrons MeSH
- Gamma Rays MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Germline genome defense evolves to recognize and suppress retrotransposons. One of defensive mechanisms is the PIWI-associated RNA (piRNA) pathway, which employs small RNAs for sequence-specific repression. The loss of the piRNA pathway in mice causes male sterility while females remain fertile. Unlike spermatogenic cells, mouse oocytes posses also RNA interference (RNAi), another small RNA pathway capable of retrotransposon suppression. To examine whether RNAi compensates the loss of the piRNA pathway, we produced a new RNAi pathway mutant DicerSOM and crossed it with a catalytically-dead mutant of Mili, an essential piRNA gene. Normal follicular and oocyte development in double mutants showed that RNAi does not suppress a strong ovarian piRNA knock-out phenotype. However, we observed redundant and non-redundant targeting of specific retrotransposon families illustrating stochasticity of recognition and targeting of invading retrotransposons. Intracisternal A Particle retrotransposon was mainly targeted by the piRNA pathway, MaLR and RLTR10 retrotransposons were targeted mainly by RNAi. Double mutants showed accumulations of LINE-1 retrotransposon transcripts. However, we did not find strong evidence for transcriptional activation and mobilization of retrotransposition competent LINE-1 elements suggesting that while both defense pathways are simultaneously expendable for ovarian oocyte development, yet another transcriptional silencing mechanism prevents mobilization of LINE-1 elements.
- MeSH
- Argonaute Proteins genetics MeSH
- DEAD-box RNA Helicases genetics MeSH
- RNA, Small Interfering genetics MeSH
- Mutation MeSH
- Mice MeSH
- Oocytes chemistry growth & development MeSH
- Retroelements * MeSH
- Ribonuclease III genetics MeSH
- RNA Interference * MeSH
- Signal Transduction MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
