scholarly journals Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal 15N2-diazirine molecular tags

2016 ◽  
Vol 2 (3) ◽  
pp. e1501438 ◽  
Author(s):  
Thomas Theis ◽  
Gerardo X. Ortiz ◽  
Angus W. J. Logan ◽  
Kevin E. Claytor ◽  
Yesu Feng ◽  
...  
Keyword(s):  
Nuclear Polarization ◽  
Molecular Function ◽  
Spin States ◽  
Time Constants ◽  
Biologically Relevant ◽  
Spin Order ◽  
Signal Decay ◽  
Wide Range ◽  
Cost Efficient ◽  
Biologically Relevant Molecules

Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, and applications are limited by short spin lifetimes (typically seconds) of biologically relevant molecules. We use a recently developed method, SABRE-SHEATH, to directly hyperpolarize 15N2 magnetization and long-lived 15N2 singlet spin order, with signal decay time constants of 5.8 and 23 minutes, respectively. We find >10,000-fold enhancements generating detectable nuclear MR signals that last for over an hour. 15N2-diazirines represent a class of particularly promising and versatile molecular tags, and can be incorporated into a wide range of biomolecules without significantly altering molecular function.

scholarly journals Magnetization Lifetimes Prediction and Measurements Using Long-Lived Spin States in Endogenous Molecules

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5495
Author(s):  
F. Teleanu ◽  
C. Tuță ◽  
A. Cucoanes ◽  
S. Vasilca ◽  
P. R. Vasos
Keyword(s):  
Amino Acids ◽  
Chemical Shifts ◽  
Spin Dynamics ◽  
A Priori ◽  
Biologically Relevant ◽  
Spin Order ◽  
Biologically Relevant Molecules ◽  
Radiation Treatments ◽  
Experimental Values

Nuclear magnetization storage in biologically-relevant molecules opens new possibilities for the investigation of metabolic pathways, provided the lifetimes of magnetization are sufficiently long. Dissolution-dynamic nuclear polarization-based spin-order enhancement, sustained by long-lived states can measure the ratios between concentrations of endogenous molecules on a cellular pathway. These ratios can be used as meters of enzyme function. Biological states featuring intracellular amino-acid concentrations that are depleted or replenished in the course of in-cell or in-vivo tests of drugs or radiation treatments can be revealed. Progressing from already-established long-lived states, we investigated related spin order in the case of amino acids and other metabolites featuring networks of coupled spins counting up to eight nuclei. We detail a new integrated theoretical approach between quantum chemistry simulations, chemical shifts, J-couplings information from databanks, and spin dynamics calculations to deduce a priori magnetization lifetimes in biomarkers. The lifetimes of long-lived states for several amino acids were also measured experimentally in order to ascertain the approach. Experimental values were in fair agreement with the computed ones and prior data in the literature.

Multi-component reactions for the synthesis of biologically relevant molecules under environmentally benign conditions

2021 ◽  
Vol 25 ◽  
Author(s):  
Ranjay Shaw ◽  
Amr Elagamy ◽  
Ismail Althagafi ◽  
Akhilesh Kumar Srivastava ◽  
Ramendra Pratap
Keyword(s):  
Review Article ◽  
Toxic Waste ◽  
Environmentally Benign ◽  
Multicomponent Synthesis ◽  
Chemical Methods ◽  
Benign Condition ◽  
Biologically Relevant ◽  
Solvent Free Conditions ◽  
Ultrasound Assisted ◽  
Biologically Relevant Molecules

: Heterocycles are the most important skeleton as they are biologically and medicinally significant. Various chemical methods have been utilized for their synthesis. Among them, environmentally benign condition are most important as they produce less toxic waste and requires less toxic solvents and reagents. There is various literature available on sustainable and multicomponent synthetic. However, it is difficult for the researcher to keep up with the research. Therefore, a review article in the sustainable and multicomponent synthesis of heterocycle was highly required. Herein, we have compiled the literature related to multicomponent reaction under solvent-free conditions, ultrasound-assisted, water or ionic liquid mediated conditions.

scholarly journals Voltage-gated transient currents in bovine adrenal fasciculata cells. I. T-type Ca2+ current.

1993 ◽  
Vol 102 (2) ◽  
pp. 217-237 ◽  
Author(s):  
B Mlinar ◽  
B A Biagi ◽  
J J Enyeart
Keyword(s):  
Time Constant ◽  
Low Voltage ◽  
Zona Fasciculata ◽  
Patch Clamp Technique ◽  
Time Constants ◽  
Voltage Gated ◽  
Wide Range ◽  
Boltzmann Function ◽  
Voltage Dependent ◽  
Ca2 Channels

The whole cell version of the patch clamp technique was used to identify and characterize voltage-gated Ca2+ channels in enzymatically dissociated bovine adrenal zona fasciculata (AZF) cells. The great majority of cells (84 of 86) expressed only low voltage-activated, rapidly inactivating Ca2+ current with properties of T-type Ca2+ current described in other cells. Voltage-dependent activation of this current was fit by a Boltzmann function raised to an integer power of 4 with a midpoint at -17 mV. Independent estimates of the single channel gating charge obtained from the activation curve and using the "limiting logarithmic potential sensitivity" were 8.1 and 6.8 elementary charges, respectively. Inactivation was a steep function of voltage with a v1/2 of -49.9 mV and a slope factor K of 3.73 mV. The expression of a single Ca2+ channel subtype by AZF cells allowed the voltage-dependent gating and kinetic properties of T current to be studied over a wide range of potentials. Analysis of the gating kinetics of this Ca2+ current indicate that T channel activation, inactivation, deactivation (closing), and reactivation (recovery from inactivation) each include voltage-independent transitions that become rate limiting at extreme voltages. Ca2+ current activated with voltage-dependent sigmoidal kinetics that were described by an m4 model. The activation time constant varied exponentially at test potentials between -30 and +10 mV, approaching a voltage-independent minimum of 1.6 ms. The inactivation time constant (tau i) also decreased exponentially to a minimum of 18.3 ms at potentials positive to 0 mV. T channel closing (deactivation) was faster at more negative voltages; the deactivation time constant (tau d) decreased from 8.14 +/- 0.7 to 0.48 +/- 0.1 ms at potentials between -40 and -150 mV. T channels inactivated by depolarization returned to the closed state along pathways that included two voltage-dependent time constants. tau rec-s ranged from 8.11 to 4.80 s when the recovery potential was varied from -50 to -90 mV, while tau rec-f decreased from 1.01 to 0.372 s. At potentials negative to -70 mV, both time constants approached minimum values. The low voltage-activated Ca2+ current in AZF cells was blocked by the T channel selective antagonist Ni2+ with an IC50 of 20 microM. At similar concentrations, Ni2+ also blocked cortisol secretion stimulated by adrenocorticotropic hormone. Our results indicate that bovine AZF cells are distinctive among secretory cells in expressing primarily or exclusively T-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Cooperative subunit dynamics modulate p97 function

2018 ◽  
Vol 116 (1) ◽  
pp. 158-167 ◽  
Author(s):  
Rui Huang ◽  
Zev A. Ripstein ◽  
John L. Rubinstein ◽  
Lewis E. Kay
Keyword(s):  
Bound State ◽  
Nmr Studies ◽  
Biologically Relevant ◽  
Aaa Atpase ◽  
Cellular Processes ◽  
Allosteric Communication ◽  
Functional Dynamics ◽  
Nmr Study ◽  
Wide Range

p97 is an essential hexameric AAA+ ATPase involved in a wide range of cellular processes. Mutations in the enzyme are implicated in the etiology of an autosomal dominant neurological disease in which patients are heterozygous with respect to p97 alleles, containing one copy each of WT and disease-causing mutant genes, so that, in vivo, p97 molecules can be heterogeneous in subunit composition. Studies of p97 have, however, focused on homohexameric constructs, where protomers are either entirely WT or contain a disease-causing mutation, showing that for WT p97, the N-terminal domain (NTD) of each subunit can exist in either a down (ADP) or up (ATP) conformation. NMR studies establish that, in the ADP-bound state, the up/down NTD equilibrium shifts progressively toward the up conformation as a function of disease mutant severity. To understand NTD functional dynamics in biologically relevant p97 heterohexamers comprising both WT and disease-causing mutant subunits, we performed a methyl-transverse relaxation optimized spectroscopy (TROSY) NMR study on a series of constructs in which only one of the protomer types is NMR-labeled. Our results show positive cooperativity of NTD up/down equilibria between neighboring protomers, allowing us to define interprotomer pathways that mediate the allosteric communication between subunits. Notably, the perturbed up/down NTD equilibrium in mutant subunits is partially restored by neighboring WT protomers, as is the two-pronged binding of the UBXD1 adaptor that is affected in disease. This work highlights the plasticity of p97 and how subtle perturbations to its free-energy landscape lead to significant changes in NTD conformation and adaptor binding.

scholarly journals A Novel Adaptive Pixels Segmentation Algorithm for Pavement Crack Detection

2021 ◽  
Author(s):  
Nima Safaei ◽  
Omar Smadi ◽  
Babak Safaei ◽  
Arezoo Masoud
Keyword(s):  
Crack Detection ◽  
Low Cost ◽  
Local Level ◽  
Cost Effective ◽  
Segmentation Algorithm ◽  
Pavement Maintenance ◽  
Detection Systems ◽  
Wide Range ◽  
Cost Efficient ◽  
Pavement Crack Detection

<p>Cracks considerably reduce the life span of pavement surfaces. Currently, there is a need for the development of robust automated distress evaluation systems that comprise a low-cost crack detection method for performing fast and cost-effective roadway health monitoring practices. Most of the current methods are costly and have labor-intensive learning processes, so they are not suitable for small local-level projects with limited resources or are only usable for specific pavement types.</p> <p>This paper proposes a new method that uses an improved version of the weighted neighborhood pixels segmentation algorithm to detect cracks in 2-D pavement images. This method uses the Gaussian cumulative density function as the adaptive threshold to overcome the drawback of fixed thresholds in noisy environments. The proposed algorithm was tested on 300 images containing a wide range of noise representative of different noise conditions. This method proved to be time and cost-efficient as it took less than 3.15 seconds per 320 × 480 pixels image for a Xeon (R) 3.70 GHz CPU processor to determine the detection results. This makes the model a perfect choice for county-level pavement maintenance projects requiring cost-effective pavement crack detection systems. The validation results were promising for the detection of low to severe-level cracks (Accuracy = 97.3%, Precision = 79.21%, Recall= 89.18% and F<sub>1</sub> score = 83.9%).</p>

scholarly journals Enantioselective organocatalysis in the synthesis of biologically relevant compounds

2016 ◽  
Author(s):  
Lukasz Albrecht
Keyword(s):  
Organic Chemistry ◽  
Amino Acids ◽  
Organic Molecules ◽  
Asymmetric Induction ◽  
Chiral Catalyst ◽  
Biologically Relevant ◽  
Enantioselective Reactions ◽  
Asymmetric Organocatalysis ◽  
Biologically Relevant Molecules ◽  
Operational Simplicity

The development of methods for the preparation of biologically relevant compounds in an enantiomerically enriched form constitutes one of the most significant tasks in the contemporary organic chemistry. In particular, enantioselective reactions where prochiral substrates are converted into enantiomerically enriched products in the presence of chiral catalyst are of great importance. Recently, asymmetric organocatalysis, where simple organic molecules are used as catalysts of various enantiodifferentiating reactions, has become a highly useful synthetic tool enabling for the efficient asymmetric induction based on diverse activation modes. Herein, we report our studies on organocatalytic, enantioselective strategies for the synthesis of biologically relevant molecules such as: quaternary α-amino acids and their isoelectronic analogs α-aminophosphonates, benzo[1,5]oxazocines, α-methylidene-δ-lactones, α-alkylidene-ketones, furfural derivatives, and benzothiophenes. The devised approaches utilize readily available chiral organocatalysts to control stereo-chemical reaction outcomes. Operational simplicity, efficiency and high enantio- and diastereoselectivities are the main benefits of the developed strategies.

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