scholarly journals Highly sensitive control of transcriptional activity by factor heterodimerization

1994 ◽  
Vol 301 (1) ◽  
pp. 9-12 ◽  
Author(s):  
S Swillens ◽  
I Pirson

Several molecular mechanisms have been proposed to explain highly sensitive controls of cellular functions by effector molecules. Here we study an equilibrium model describing the regulation of transcriptional activity through the heterodimerization of transcription factors. We demonstrate that this model involves a new type of biochemical control which accounts for a very high sensitivity.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Eisaku Katayama ◽  
Yuhei O. Tahara ◽  
Clothilde Bertin ◽  
Satoshi Shibata

Abstract 3-D Structural information is essential to elucidate the molecular mechanisms of various biological machineries. Quick-Freeze Deep-Etch-Replica Electron Microscopy is a unique technique to give very high-contrast surface profiles of extra- and intra-cellular apparatuses that bear numerous cellular functions. Though the global architecture of those machineries is primarily required to understand their functional features, it is difficult or even impossible to depict side- or highly-oblique views of the same targets by usual goniometry, inasmuch as the objects (e.g. motile microorganisms) are placed on conventional flat substrates. We introduced silica-beads as an alternative substrate to solve such crucial issue. Elongated Flavobacterium and globular Mycoplasmas cells glided regularly along the bead’s surface, similarly to those on a flat substrate. Quick-freeze replicas of those cells attached to the beads showed various views; side-, oblique- and frontal-views, enabling us to study not only global but potentially more detailed morphology of complicated architecture. Adhesion of the targets to the convex surface could give surplus merits to visualizing intriguing molecular assemblies within the cells, which is relevant to a variety of motility machinery of microorganisms.


2005 ◽  
Vol 16 (6) ◽  
pp. 2660-2669 ◽  
Author(s):  
Jean Savare ◽  
Nathalie Bonneaud ◽  
Franck Girard

Sry high mobility group (HMG) box (Sox) transcription factors are involved in the development of central nervous system (CNS) in all metazoans. Little is known on the molecular mechanisms that regulate their transcriptional activity. Covalent posttranslational modification by small ubiquitin-like modifier (SUMO) regulates several nuclear events, including the transcriptional activity of transcription factors. Here, we demonstrate that SoxNeuro, an HMG box-containing transcription factor involved in neuroblast formation in Drosophila, is a substrate for SUMO modification. SUMOylation assays in HeLa cells and Drosophila S2 cells reveal that lysine 439 is the major SUMO acceptor site. The sequence in SoxNeuro targeted for SUMOylation, IKSE, is part of a small inhibitory domain, able to repress in cis the activity of two adjacent transcriptional activation domains. Our data show that SUMO modification represses SoxNeuro transcriptional activity in transfected cells. Overexpression in Drosophila embryos of a SoxN form that cannot be targeted for SUMOylation strongly impairs the development of the CNS, suggesting that SUMO modification of SoxN is crucial for regulating its activity in vivo. Finally, we present evidence that SUMO modification of group B1 Sox factors was conserved during evolution, because Sox3, the human counterpart of SoxN, is also negatively regulated through SUMO modification.


Author(s):  
Zhong-Zheng Ding ◽  
Guang-Song Zheng ◽  
Qing Lou ◽  
Jiang-Fan Han ◽  
Meng-Yuan Wu ◽  
...  

Abstract Excellent luminescent materials are essential for high-performance fluorescent nanosensors. Here, a new-type self-calibrated humidity sensor has been established through monitoring the fluorescent color change of carbon dots (CDs) confined in sodium hydroxide (CDs@NaOH). The CDs are prepared by a facile and rapid microwave assisted heating method using citric acid, urea, and NaOH as precursors. The confinement effect from NaOH has reduced the nonradiative transition and suppressed the aggregation-induced quenching of the CDs in solid. Compared with other sensors based on CD fluorescent visualization, the sensor has good linearity and wide humidity detection range from 6.9% to 95.4%. With the increased relative humidity, the fluorescence color of the sensor change from green to blue. The proposed sensing mechanism is due to the breaking and reforming of hydrogen bonds and proton transfer occurring at the CD-NaOH matrix interfaces. This finding suggests a potential role for the spatial confinement effect and may provide an avenue for developing highly sensitive humidity readouts.


2014 ◽  
Vol 29 (1) ◽  
pp. e55-e61 ◽  
Author(s):  
Francesca Messa ◽  
Federica Tonissi ◽  
Enrico Millo ◽  
Enrico Bracco ◽  
Silvana Ungari ◽  
...  

The detection of somatic mutations in a tumor represents a valuable tool for tumor characterization and provides the clinicians with information for setting up the most appropriate therapy. KRAS mutations in codons 12 and 13 are important biomarkers routinely analyzed in the clinic for the management of anti-EGFR treatment in colorectal carcinoma (CRC). Here we report a sensitive and inexpensive assay for KRAS mutations based on a PNA-mediated PCR clamping. The assay displays very high sensitivity (0.7%) and specificity (96.7%) when compared to traditional sequencing (SS) and pyrosequencing (PS), two of the most commonly and routinely used methods employed today by diagnostic laboratories. Furthermore, the PNA assay requires only basic and low-cost laboratory equipment, in contrast with all the most recent PCR-based technologies, which are highly sensitive but also much more expensive. Finally, despite the PNA assay does not allow for the definition of specific mutations, it is the cheapest and easiest screening method to firstly stratify wild-type and mutated patients, information that is strictly necessary to clinicians for the management of CRC and anti-EGFR treatment.


2014 ◽  
Vol 787 ◽  
pp. 378-382 ◽  
Author(s):  
Masaya Ichimura ◽  
Dengbaoleer Ao

Highly sensitive room temperature hydrogen sensors based on undoped and Fe-doped SnO2 films were fabricated. The SnO2 films were deposited by the photochemical deposition using an aqueous solution containing SnSO4. For deposition of doped and undoped SnO2 films, a small amount of an aqueous solution was dropped on a glass substrate and irradiated by UV light. The sensors annealed at 200oC showed extremely high sensitivity to hydrogen, but the initial resistance was very high. The sensors annealed at 400oC had a much lower resistance, and thus the sensor response was able to be measured even by a pocket multimeter. The Fe-doped sample showed higher sensitivity compared with the undoped sample.


2021 ◽  
Author(s):  
Anita Badbaran ◽  
Reiner Mailer ◽  
Christine Dahlke ◽  
Jannis Woens ◽  
Anahita Fathi ◽  
...  

AbstractVaccination with the adenoviral-vector based Astra Zeneca ChAdOx1 nCov-19 vaccine is efficient and safe. However, in rare cases vaccinated individuals developed life-threatening thrombotic complications, including thrombosis in cerebral sinus and splanchnic veins. Monitoring of the applied vector in vivo represents an important precondition to study the molecular mechanisms underlying vaccine-driven adverse effects now referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). We previously have shown that digital PCR is an excellent tool to quantify transgene copies in vivo. Here we present a highly sensitive digital PCR for in-situ quantification of ChAdOx1 nCoV-19 copies. Using this method, we quantified vector copies in human serum 24, 72 and 168 hours post vaccination, and in a variety of murine tissues in an experimental vaccination model 30 minutes post injection. We describe a method for high-sensitivity quantitative detection of ChAdOx1 nCoV-19 with possible implications to elucidate the mechanisms of severe ChAdOx1 nCov-19 vaccine complications.


2021 ◽  
Author(s):  
Zaky A. Zaky ◽  
Arafa H. Aly

Abstract In this paper, a Tamm plasmons resonance-based sensor is theoretically studied to calculate the salinity of seawater as well as a temperature sensor based on photonic crystals. The transfer matrix method (TMM) is used to systematically study and analyze the reflected s-polarized electromagnetic waves from the sensing structure. The proposed structure composes of prism/Au/water/(Si/SiO2)N/Si. The sensitivity, figure-of-merit, quality factor, and detection limit of the sensors are improved by optimizing the thickness of the seawater layer, incident angle, salinity concentration, and temperature. The proposed salinity sensor records a very high sensitivity of 8.5x104 nm/RIU and quality factor of 3x103, and a very low detection limit of 10-7 nm. Besides, the suggested temperature sensor achieves high sensitivity (from 2.8 nm/˚C to 10.8 nm/˚C), high-quality factor of 3.5x103, and a very low detection limit of 3x10-7 nm. These results indicate that the proposed sensor is a strong candidate for salinity and temperature measurements.


2008 ◽  
Vol 389 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Daniel G. Sedding

Abstract Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxidative stress and ageing. FoxOs are regulated by a variety of different growth factors and hormones, and their activity is tightly controlled by post-translational modifications, including phosphorylation, acetylation, ubiquitination and interaction with different proteins and transcription factors. This brief review focuses on the molecular mechanisms, cellular effects and resulting organismal phenotypes generated by differentially regulated FoxO proteins and discusses our current understanding of the role of FoxOs in disease and ageing processes.


2021 ◽  
Vol 1 (19) ◽  
pp. 234-236
Author(s):  
A.I. Zilberman ◽  
I.I. Vashkevich ◽  
O.V. Sviridov

Specific immunoreagents have been obtained and a direct enzyme-linked immunosorbent assay with a very high sensitivity to penicillins in standard solutions (0.06 ng/ml) as well as in the samples of milk (0.3 μg/kg) and meat (2.4 μg/kg) has been developed.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kangni Chen ◽  
Yanbo Li ◽  
Jinyan Shang ◽  
Chao Zhao ◽  
Heping Li

AbstractOzone is widely used in daily life, but studies have shown that O3 can damage human trachea and lungs, leading to diseases such as asthma, emphysema, and bronchitis. Therefore, it is of great significance to develop a simple and efficient detection method for monitoring O3 in living cells. In this study, 3-(but-3-en-1-yl)-2-(7-(but-3-en-1-yloxy)-2-oxo-2H-chromen-3-yl)benzo[d]thiazol-3-ium (BCT) as a new type of water-soluble fluorescent probe was synthesized by substitution reaction of 4-bromo-1-butene and hydroxycoumarin-benzothiazole derivatives, which can specifically detect ozone in aqueous solution. The interaction of ozone on the probe can be completed within 20 min, the fluorescence intensity is significantly enhanced, and it has the advantages of high sensitivity (detection limit LOD = 43 nM). The influence of pH on the fluorescent performance of BCT shows that the probe with super stability under weak alkali and acidic environment, which provides the necessary conditions for its detection of ozone in physiological system detection. Therefore, BCT is expected to become an effective tool for detecting ozone in cellular organisms.


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