A spectroscopic case for SPSi detection: The third-row in a single molecule

2016 ◽  
Vol 145 (12) ◽  
pp. 124311 ◽  
Author(s):  
Brian Finney ◽  
Ryan C. Fortenberry ◽  
Joseph S. Francisco ◽  
Kirk A. Peterson
Keyword(s):  
Single Molecule ◽  
The Third

scholarly journals Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase

2020 ◽  
Author(s):  
David Mengel ◽  
Wen Liu ◽  
Robert J. Glynn ◽  
Dennis J. Selkoe ◽  
Andre Strydom ◽  
...  
Keyword(s):  
Young Adults ◽  
Down Syndrome ◽  
Single Molecule ◽  
Neuronal Loss ◽  
Later Life ◽  
Adolescents And Young Adults ◽  
Older Individuals ◽  
Plasma Biomarkers ◽  
The Third ◽  
Aβ Amyloid

Abstract Background Down syndrome (DS) is the most common genetic cause of Alzheimer’s Disease (AD), but diagnosis of AD in DS is challenging due to the intellectual disability which accompanies DS. When disease-modifying agents for AD are approved, reliable biomarkers will be required to identify when and how long people with DS should undergo treatment. Three cardinal neuropathological features characterize AD, and AD in DS – Aβ amyloid plaques, tau neurofibrillary tangles, and neuronal loss. Here, we quantified plasma biomarkers of all 3 neuropathological features in a large cohort of people with DS aged from 3 months to 68 years. Methods Using ultra-sensitive single molecule array (Simoa) assays, we measured 3 analytes (Aβ42, NfL, and tau) in plasmas of 100 individuals with DS and 100 age- and sex-matched controls. Tau was measured using an assay (NT1) which detects forms of tau containing at least residues 6-198, and the stability of the 3 analytes was established using plasma from ten healthy volunteers collected at 6 intervals over a five day period. Results High Aβ42 and NT1 tau, and low NfL, were observed in infants. Across all ages, Aβ42 levels were higher in DS than controls. Levels of Aβ42 decreased with age in both DS and controls, but this decrease was greater in DS than controls and became prominent in the third decade of life. NT1 tau fell in adolescents and young adults, but increased in older individuals with DS. NfL levels were low in infants, children, adolescents and young adults, but thereafter increased in DS compared to controls. Conclusions High levels of Aβ42 and tau in both young controls and DS suggest these proteins are produced by normal physiological processes, whereas, the changes seen in later life are consistent with emergence of pathological alterations. Our plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e. 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS. Application of the assays used here to longitudinal studies of individuals with DS aged 20 to 50 years of age, should further validate the use of these biomarkers, and in time may allow identification and monitoring of people with DS best suited for treatment with emerging AD therapies.

D4h Local Symmetric dysprosium(III) Single-Molecule Magnet with Energy Barrier Exceeding 2000 K

2020 ◽  
Author(s):  
Xia-Li Ding ◽  
Yuan-Qi Zhai ◽  
Tian Han ◽  
Wei-Peng Chen ◽  
You-Song Ding ◽  
...  
Keyword(s):  
Single Molecule ◽  
Energy Barrier ◽  
Local Symmetry ◽  
Single Molecule Magnets ◽  
Single Molecule Magnet ◽  
The Third ◽  
Type Symmetry

<p><a></a><a></a><a><b>Three six-coordinate Dy(III) single-molecule magnets (SMMs) [Dy(O<sup>t</sup>Bu)<sub>2</sub>(L)<sub>4</sub>]<sup>+</sup> with <i>D</i><sub>4h</sub> local symmetry are obtained by optimising the equatorial ligands. Compound 1 where L = 4-phenylpyridine shows an energy barrier (<i>U</i><sub>eff</sub>) of 2075(11) K, which is the third largest <i>U</i><sub>eff</sub>, and the first <i>U</i><sub>eff</sub> > 2000 K for SMMs with axial-type symmetry so far.</b></a></p>

scholarly journals Simple mechanism whereby the F1-ATPase motor rotates with near-perfect chemomechanical energy conversion

2015 ◽  
Vol 112 (31) ◽  
pp. 9626-9631 ◽  
Author(s):  
Ei-ichiro Saita ◽  
Toshiharu Suzuki ◽  
Kazuhiko Kinosita ◽  
Masasuke Yoshida
Keyword(s):  
Physical Model ◽  
Single Molecule ◽  
Atp Hydrolysis ◽  
Rotation Angle ◽  
Mechanical Work ◽  
F1 Atpase ◽  
The Third ◽  
Γ Subunit ◽  
Simple Physical Model ◽  
Central Shaft

F1-ATPase is a motor enzyme in which a central shaft γ subunit rotates 120° per ATP in the cylinder made of α3β3 subunits. During rotation, the chemical energy of ATP hydrolysis (ΔGATP) is converted almost entirely into mechanical work by an elusive mechanism. We measured the force for rotation (torque) under various ΔGATP conditions as a function of rotation angles of the γ subunit with quasi-static, single-molecule manipulation and estimated mechanical work (torque × traveled angle) from the area of the function. The torque functions show three sawtooth-like repeats of a steep jump and linear descent in one catalytic turnover, indicating a simple physical model in which the motor is driven by three springs aligned along a 120° rotation angle. Although the second spring is unaffected by ΔGATP, activation of the first spring (timing of the torque jump) delays at low [ATP] (or high [ADP]) and activation of the third spring delays at high [Pi]. These shifts decrease the size and area of the sawtooth (magnitude of the work). Thus, F1-ATPase responds to the change of ΔGATP by shifting the torque jump timing and uses ΔGATP for the mechanical work with near-perfect efficiency.

scholarly journals Statistical properties of the dichotomous noise generated in biochemical processes

2008 ◽  
Vol 13 (4) ◽  
Author(s):  
Michał Kurzyński
Keyword(s):  
Autocorrelation Function ◽  
Single Molecule ◽  
Stochastic Dynamics ◽  
Statistical Properties ◽  
Native State ◽  
Third Order ◽  
Dichotomous Noise ◽  
Biochemical Processes ◽  
Conformational Substates ◽  
The Third

AbstractDichotomous noise detected with the help of various single-molecule techniques convincingly reveals the actual occurrence of a multitude of conformational substates composing the native state of proteins. The nature of the stochastic dynamics of transitions between these substates is determined by the particular statistical properties of the noise observed. These involve nonexponential and possibly oscillatory time decay of the second order autocorrelation function, its relation to the third order autocorrelation function, and a relationship to dwell-time distribution densities and their correlations. Processes gated by specific conformational substates are distinguished from those with fluctuating barriers. This study throws light on the intriguing matter of the possibility of multiple stepping of the myosin motor along the actin filament per ATP molecule hydrolyzed.

scholarly journals Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ1-42 decrease with age, whereas NT1 tau and NfL increase

2019 ◽  
Author(s):  
David Mengel ◽  
Wen Liu ◽  
Robert J. Glynn ◽  
Dennis J. Selkoe ◽  
Andre Strydom ◽  
...  
Keyword(s):  
Young Adults ◽  
Down Syndrome ◽  
Single Molecule ◽  
Neuronal Loss ◽  
Later Life ◽  
Adolescents And Young Adults ◽  
Older Individuals ◽  
Plasma Biomarkers ◽  
The Third ◽  
Aβ Amyloid

Abstract Background: Down syndrome (DS) is the most common genetic cause of Alzheimer’s Disease (AD), but diagnosis of AD in DS is challenging due to the intellectual disability which accompanies DS. When disease-modifying agents for AD are approved, reliable biomarkers will be required to identify when and how long people with DS should undergo treatment. Three cardinal neuropathological features characterize AD, and AD in DS – Aβ amyloid plaques, tau neurofibrillary tangles, and neuronal loss. Here, we quantified plasma biomarkers of all 3 neuropathological features in a large cohort of people with DS aged from 3 months to 68 years.Methods: Using ultra-sensitive single molecule array (Simoa) assays, we measured 3 analytes in plasmas of 100 individuals with DS and 100 age- and sex-matched controls. The analytes were: Aβ1-42, NfL, and tau. The latter was measured by an assay (NT1) which detects forms of tau containing at least residues 6-198.Results: High Aβ1-42 and NT1 tau, and low NfL, were observed in infants. Across all ages, Aβ1-42 levels were higher in DS than controls. Levels of Aβ1-42 decreased with age in both DS and controls, but this decrease was greater in DS than controls and became prominent in the third decade of life. NT1 tau fell in adolescents and young adults, but increased in older individuals with DS. NfL levels were low in infants, children, adolescents and young adults, but thereafter increased in DS compared to controls. Conclusions: High levels of Aβ1-42 and tau in both young controls and DS suggest these proteins are produced by normal physiological processes, whereas, the changes seen in later life are consistent with emergence of pathological alterations. Our plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e. 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS. Application of the assays used here to longitudinal studies of individuals with DS aged 20 to 50 years of age, should further validate the use of these biomarkers, and in time may allow identification and monitoring of people with DS best suited for treatment with emerging AD therapies.

scholarly journals D4h Local Symmetric dysprosium(III) Single-Molecule Magnet with Energy Barrier Exceeding 2000 K

2020 ◽  
Author(s):  
Xia-Li Ding ◽  
Yuan-Qi Zhai ◽  
Tian Han ◽  
Wei-Peng Chen ◽  
You-Song Ding ◽  
...  
Keyword(s):  
Single Molecule ◽  
Energy Barrier ◽  
Local Symmetry ◽  
Single Molecule Magnets ◽  
Single Molecule Magnet ◽  
The Third ◽  
Type Symmetry

<p><a></a><a></a><a><b>Three six-coordinate Dy(III) single-molecule magnets (SMMs) [Dy(O<sup>t</sup>Bu)<sub>2</sub>(L)<sub>4</sub>]<sup>+</sup> with <i>D</i><sub>4h</sub> local symmetry are obtained by optimising the equatorial ligands. Compound 1 where L = 4-phenylpyridine shows an energy barrier (<i>U</i><sub>eff</sub>) of 2075(11) K, which is the third largest <i>U</i><sub>eff</sub>, and the first <i>U</i><sub>eff</sub> > 2000 K for SMMs with axial-type symmetry so far.</b></a></p>

scholarly journals Signatures and mechanisms of efficacious therapeutic ribonucleotides against SARS-CoV-2 revealed by analysis of its replicase using magnetic tweezers

2020 ◽  
Author(s):  
Mona Seifert ◽  
Subhas Chandra Bera ◽  
Pauline van Nies ◽  
Robert N. Kirchdoerfer ◽  
Ashleigh Shannon ◽  
...  
Keyword(s):  
Single Molecule ◽  
Magnetic Tweezers ◽  
Therapeutic Strategies ◽  
High Fidelity ◽  
Experimental Paradigm ◽  
Nucleotide Analogs ◽  
The Third ◽  
Nucleotide Addition ◽  
A Chain ◽  
Chain Terminator

SummaryCoronavirus Disease 2019 (COVID-19) results from an infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the third coronavirus outbreak to plague humanity this century. Currently, the most efficacious therapeutic against SARS-CoV-2 infection is the Remdesivir (RDV), an adenine-like ribonucleotide analogue that is very efficiently incorporated by the SARS-CoV-2 replicase. Understanding why RDV is so well incorporated will facilitate development of even more effective therapeutics. Here, we have applied a high-throughput, single-molecule, magnetic-tweezers platform to study thousands of cycles of nucleotide addition by the SARS-CoV-2 replicase in the absence and presence of RDV, a Favipiravir-related analog (T-1106), and the endogenously produced ddhCTP. Our data are consistent with two parallel catalytic pathways of the replicase: a high-fidelity catalytic (HFC) state and a low-fidelity catalytic (LFC) state, the latter allowing the slow incorporation of both cognate and non-cognate nucleotides. ddhCTP accesses HFC, T-1106 accesses LFC as a non-cognate nucleotide, while RDV efficiently accesses both LFC pathway. In contrast to previous reports, we provide unequivocal evidence against RDV functioning as a chain terminator. We show that RDV incorporation transiently stalls the replicase, only appearing as termination events when traditional, gel-based assays are used. The efficiency of ddhCTP utilization by the SARS-CoV-2 replicase suggests suppression of its synthesis during infection, inspiring new therapeutic strategies. Use of this experimental paradigm will be essential to the development of therapeutic nucleotide analogs targeting polymerases.

Progress report on 21-cm observations at low latitude between longitudes (l 11) 0° and 66°

1967 ◽  
Vol 31 ◽  
pp. 177-179
Author(s):  
W. W. Shane
Keyword(s):  
Preliminary Report ◽  
Progress Report ◽  
Galactic Centre ◽  
Low Latitude ◽  
The Third ◽  
Introductory Lecture ◽  
Centre Region

In the course of several 21-cm observing programmes being carried out by the Leiden Observatory with the 25-meter telescope at Dwingeloo, a fairly complete, though inhomogeneous, survey of the regionl11= 0° to 66° at low galactic latitudes is becoming available. The essential data on this survey are presented in Table 1. Oort (1967) has given a preliminary report on the first and third investigations. The third is discussed briefly by Kerr in his introductory lecture on the galactic centre region (Paper 42). Burton (1966) has published provisional results of the fifth investigation, and I have discussed the sixth in Paper 19. All of the observations listed in the table have been completed, but we plan to extend investigation 3 to a much finer grid of positions.

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