scholarly journals Abiotic Reactivity of De Novo Designed Artificial Copper Peptides (ArCuPs): The Case of C-H Activation

2022 ◽  
Author(s):  
Divyansh Prakash ◽  
Suchitra Mitra ◽  
Morgan Murphy ◽  
Saumen Chakraborty
Keyword(s):  
Steric Effect ◽  
De Novo ◽  
Outer Sphere ◽  
The Other ◽  
Easy Access ◽  
Oxygen Species ◽  
Redox Potentials ◽  
Spectroscopic Feature ◽  
Detailed Assessment ◽  
Active Variant

We report a series of de novo designed Artificial Cu Peptides (ArCuPs) that oxidize and peroxygenate C-H bonds of model abiotic substrates via electrochemically generated Cu-oxygen species using H2O2 as the terminal oxidant, akin to native Cu enzymes. Detailed assessment of kinetic parameters established the catalytic nature of the ArCuPs. Selective alteration of outer sphere steric at the d layers above and below the Cu site allows facilitated access of substrates, where a more pronounced effect on catalysis is observed when space is created at the d layer below the Cu site via Ile to Ala mutation producing a kcat of 6.2 s-1, TONmax of 14800 and catalytic proficiency (kcat/KM/kuncat) of 340 M-1 for the oxidation of benzyl alcohol. Independent spectroscopic studied revealed that the rate of formation of the Cu-oxygen species and the spectroscopic feature of the most active variant is distinct compared to the other ArCuPs. Systematic alteration of outer sphere hydrophobicity led to a correlated tuning of the T2 Cu site redox potentials by ~80 mV. The enhanced activity of the ArCuP variant is attributed to a combination of steric effect that allows easy access of substrates, the nature of Cu-oxygen species, and stability of this construct compared to others, where Ile to Ala mutation unexpectedly leads to a higher thermostability which is further augmented by Cu binding.

Abiotic Reactivity of De Novo Designed Artificial Copper Peptides (ArCuPs): The Case of C-H Activation

2022 ◽  
Author(s):  
Divyansh Prakash ◽  
Suchitra Mitra ◽  
Morgan Murphy ◽  
Saumen Chakraborty
Keyword(s):  
Steric Effect ◽  
De Novo ◽  
Outer Sphere ◽  
The Other ◽  
Easy Access ◽  
Oxygen Species ◽  
Redox Potentials ◽  
Spectroscopic Feature ◽  
Detailed Assessment ◽  
Active Variant

We report a series of de novo designed Artificial Cu Peptides (ArCuPs) that oxidize and peroxygenate C-H bonds of model abiotic substrates via electrochemically generated Cu-oxygen species using H2O2 as the terminal oxidant, akin to native Cu enzymes. Detailed assessment of kinetic parameters established the catalytic nature of the ArCuPs. Selective alteration of outer sphere steric at the d layers above and below the Cu site allows facilitated access of substrates, where a more pronounced effect on catalysis is observed when space is created at the d layer below the Cu site via Ile to Ala mutation producing a kcat of 6.2 s-1, TONmax of 14800 and catalytic proficiency (kcat/KM/kuncat) of 340 M-1 for the oxidation of benzyl alcohol. Independent spectroscopic studied revealed that the rate of formation of the Cu-oxygen species and the spectroscopic feature of the most active variant is distinct compared to the other ArCuPs. Systematic alteration of outer sphere hydrophobicity led to a correlated tuning of the T2 Cu site redox potentials by ~80 mV. The enhanced activity of the ArCuP variant is attributed to a combination of steric effect that allows easy access of substrates, the nature of Cu-oxygen species, and stability of this construct compared to others, where Ile to Ala mutation unexpectedly leads to a higher thermostability which is further augmented by Cu binding.

scholarly journals Abiotic Reactivity of De Novo Designed Artificial Copper Peptides (ArCuPs): The Case of C-H Activation

2022 ◽  
Author(s):  
Divyansh Prakash ◽  
Suchitra Mitra ◽  
Morgan Murphy ◽  
Saumen Chakraborty
Keyword(s):  
Steric Effect ◽  
De Novo ◽  
Outer Sphere ◽  
The Other ◽  
Easy Access ◽  
Oxygen Species ◽  
Redox Potentials ◽  
Spectroscopic Feature ◽  
Detailed Assessment ◽  
Active Variant

We report a series of de novo designed Artificial Cu Peptides (ArCuPs) that oxidize and peroxygenate C-H bonds of model abiotic substrates via electrochemically generated Cu-oxygen species using H2O2 as the terminal oxidant, akin to native Cu enzymes. Detailed assessment of kinetic parameters established the catalytic nature of the ArCuPs. Selective alteration of outer sphere steric at the d layers above and below the Cu site allows facilitated access of substrates, where a more pronounced effect on catalysis is observed when space is created at the d layer below the Cu site via Ile to Ala mutation producing a kcat of 6.2 s-1, TONmax of 14800 and catalytic proficiency (kcat/KM/kuncat) of 340 M-1 for the oxidation of benzyl alcohol. Independent spectroscopic studied revealed that the rate of formation of the Cu-oxygen species and the spectroscopic feature of the most active variant is distinct compared to the other ArCuPs. Systematic alteration of outer sphere hydrophobicity led to a correlated tuning of the T2 Cu site redox potentials by ~80 mV. The enhanced activity of the ArCuP variant is attributed to a combination of steric effect that allows easy access of substrates, the nature of Cu-oxygen species, and stability of this construct compared to others, where Ile to Ala mutation unexpectedly leads to a higher thermostability which is further augmented by Cu binding.

scholarly journals Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHP

2021 ◽  
Vol 22 (12) ◽  
pp. 6320
Author(s):  
Monia Lenzi ◽  
Veronica Cocchi ◽  
Sofia Gasperini ◽  
Raffaella Arfè ◽  
Matteo Marti ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Metabolic Activation ◽  
Fold Increase ◽  
Synthetic Cathinones ◽  
The Other ◽  
Oxygen Species ◽  
Genetic Damage ◽  
Mutagenic Potential ◽  
Tk6 Cells ◽  
Mutagenic Effects

Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35–100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure.

scholarly journals Sociocultural Context of Suicidal Behaviour in the Sundarban Region of India

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
A. N. Chowdhury ◽  
S. Banerjee ◽  
A. Brahma ◽  
A. Hazra ◽  
M. G. Weiss
Keyword(s):  
Psychiatric Diagnosis ◽  
Suicidal Behaviour ◽  
Adjustment Disorder ◽  
Community Action ◽  
Easy Access ◽  
Social Stressors ◽  
Young Females ◽  
Detailed Assessment ◽  
Self Harm

The role of mental illness in nonfatal deliberate self-harm (DSH) is controversial, especially in Asian countries. This prospective study examined the role of psychiatric disorders, underlying social and situational problems, and triggers of DSH in a sample of 89 patients hospitalised in primary care hospitals of the Sundarban Delta, India. Data were collected by using a specially designed DSH register, Explanatory Model Interview Catalogue (EMIC), and clinical interview. Psychiatric diagnosis was made following the DSM-IV guidelines. The majority of subjects were young females (74.2%) and married (65.2%). Most of them (69.7%) were uncertain about their “intention to die,” and pesticide poisoning was the commonest method (95.5%). Significant male-female differences were found with respect to education level, occupation, and venue of the DSH attempt. Typical stressors were conflict with spouse, guardians, or in-laws, extramarital affairs, chronic physical illness, and failed love affairs. The major depressive disorder (14.6%) was the commonest psychiatric diagnosis followed by adjustment disorder (6.7%); however 60.7% of the cases had no psychiatric illness. Stressful life situations coupled with easy access to lethal pesticides stood as the risk factor. The sociocultural dynamics behind suicidal behaviour and community-specific social stressors merit detailed assessment and timely psychosocial intervention. These findings will be helpful to design community-based mental health clinical services and community action in the region.

Paranemin and the organization of desmin filament networks

2001 ◽  
Vol 114 (6) ◽  
pp. 1079-1089 ◽  
Author(s):  
S.C. Schweitzer ◽  
M.W. Klymkowsky ◽  
R.M. Bellin ◽  
R.M. Robson ◽  
Y. Capetanaki ◽  
...  
Keyword(s):  
Cell Lines ◽  
Intermediate Filament ◽  
Transgene Expression ◽  
De Novo ◽  
Muscle Cells ◽  
The Other ◽  
Intermediate Filament Proteins ◽  
Mouse Fibroblasts ◽  
Filament Networks ◽  
Filament Network

De novo expression of vimentin, GFAP or peripherin leads to the assembly of an extended intermediate filament network in intermediate filament-free SW13/cl.2 cells. Desmin, in contrast, does not form extended filament networks in either SW13/cl.2 or intermediate filament-free mouse fibroblasts. Rather, desmin formed short thickened filamentous structures and prominent spot-like cytoplasmic aggregates that were composed of densely packed 9–11 nm diameter filaments. Analysis of stably transfected cell lines indicates that the inability of desmin to form extended networks is not due to a difference in the level of transgene expression. Nestin, paranemin and synemin are large intermediate filament proteins that coassemble with desmin in muscle cells. Although each of these large intermediate filament proteins colocalized with desmin when coexpressed in SW-13 cells, expression of paranemin, but not synemin or nestin, led to the formation of an extended desmin network. A similar rescue of desmin network organization was observed when desmin was coexpressed with vimentin, which coassembles with desmin, or with keratins, which formed a distinct filament network. These studies demonstrate that desmin filaments differ in their organizational properties from the other vimentin-like intermediate filament proteins and appear to depend upon coassembly with paranemin, at least when they are expressed in non-muscle cells, in order to form an extended filament network.

Plasma Oxidation Process of Silicon Surfaces Investigated by Infrared Spectroscopy

2005 ◽  
Vol 8 (1) ◽  
Author(s):  
Masanori Shinohara ◽  
Teruaki Katagiri ◽  
Keitaro Iwatsuji ◽  
Yoshinobu Matsuda ◽  
Yasuo Kimura ◽  
...  
Keyword(s):  
Oxygen Plasma ◽  
Oxidation Process ◽  
The Other ◽  
Silicon Surfaces ◽  
Infrared Absorption Spectroscopy ◽  
Oxygen Species ◽  
Plasma Oxidation ◽  
Oxidation Processes ◽  
Surface Hydrogen ◽  
Stretching Vibration

AbstractPlasma oxidation processes of hydrogen-terminated Si(100), (110), and (111) surfaces are investigated by infrared absorption spectroscopy (IRAS) in multiple internal reflection (MIR) geometry. We measured IRAS spectra of hydrogen-terminated Si surfaces exposed to oxygen-plasma in the Si-H stretching vibration region. IRAS data demonstrated that oxygen-plasma affects two influences on the Si surfaces; one is that oxygen-plasma removes surface hydrogen to oxidize the Si surfaces. The other is that it forces the hydrogen into the subsurface regions where oxygen species cannot reach. The former effect does not depend on the crystal graphic orientations, but the latter depends on it. Therefore, in order to oxidize perfectly the H-terminated Si surfaces using oxygen-plasma, the sample surfaces need to be heated so that oxygen atoms can diffuse into the subsurface regions.

scholarly journals Stentless Strategy by Drug-Coated Balloon Angioplasty following Directional Coronary Atherectomy for Left Main Bifurcation Lesion

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Norihiro Kobayashi ◽  
Masahiro Yamawaki ◽  
Shinsuke Mori ◽  
Masakazu Tsutsumi ◽  
Yohsuke Honda ◽  
...  
Keyword(s):  
De Novo ◽  
Artery Bypass ◽  
The Other ◽  
Bleeding Complications ◽  
Left Main ◽  
Other Hand ◽  
Bifurcation Lesion ◽  
Bifurcation Lesions ◽  
Directional Coronary Atherectomy ◽  
Drug Coated Balloon

Aims. We aimed to evaluate the efficacy of stentless strategy by drug-coated balloon (DCB) angioplasty following directional coronary atherectomy (DCA) for left main (LM) bifurcation lesions. Methods. A total of 38 patients who underwent DCB angioplasty following DCA for LM bifurcation lesions were retrospectively enrolled. The primary endpoint was target vessel failure (TVF) at 12 months. Secondary endpoints included procedure-related major events during the hospitalization, major adverse cardiac events at 12 months, ischemia-driven target lesion revascularization (TLR) at 12 months, and bleeding complications defined as the Bleeding Academic Research Consortium criteria ≥2 at 12 months. Results. Among these 38 lesions, 31 lesions were de novo LM bifurcation lesions and 7 lesions were stent edge restenosis at the left anterior descending (LAD) ostium. The mean % plaque area (%PA) after DCA was 44.0 ± 7.4%. TVF at 12 months occurred in 1 lesion (3.2%) of de novo LM bifurcation lesion and in 3 lesions (42.9%) of stent edge restenosis at the LAD ostium. All events of TVF were ischemia-driven TLR by percutaneous coronary intervention. Among 4 TLR cases, %PA after DCA was high (55.9%) in the de novo LM bifurcation lesions; on the other hand, %PA after DCA was low (42.4%, 38.7%, and 25.7% in the 3 cases) in stent edge restenosis at the LAD ostium. No procedure-related major events were observed during hospitalization. There was no cardiac death, no myocardial infarction, no coronary artery bypass grafting, and no bleeding complications at 12 months. Conclusions. Stentless strategy by DCB angioplasty following DCA for de novo LM bifurcation lesions resulted in acceptable outcomes. On the other hand, its efficacy was limited for stent edge restenosis at the LAD ostium even after aggressive debulking by DCA.

scholarly journals Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function

2021 ◽  
Author(s):  
Jee Hyung Sohn ◽  
Yul Ji ◽  
Chang-Yun Cho ◽  
Hahn Nahmgoong ◽  
Sangsoo Lim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Redox Potentials ◽  
Brown Adipocytes ◽  
Erk Activation ◽  
Brown Adipose ◽  
Erk Inhibition ◽  
Glucose 6 Phosphate Dehydrogenase

Reactive oxygen species (ROS) are associated with various roles of brown adipocytes. Glucose-6-phosphate dehydrogenase (G6PD) controls cellular redox potentials by producing NADPH. Although G6PD upregulates cellular ROS levels in white adipocytes, the roles of G6PD in brown adipocytes remain elusive. Here, we found that G6PD defect in brown adipocytes impaired thermogenic function through excessive cytosolic ROS accumulation. Upon cold exposure, G6PD-deficient mutant (G6PD<sup>mut</sup>) mice exhibited cold intolerance and downregulated thermogenic gene expression in brown adipose tissue (BAT). In addition, G6PD-deficient brown adipocytes had increased cytosolic ROS levels, leading to ERK activation. In BAT of G6PD<sup>mut</sup> mice, administration of antioxidant restored the thermogenic activity by potentiating thermogenic gene expression and relieving ERK activation. Consistently, body temperature and thermogenic execution were rescued by ERK inhibition in cold-exposed G6PD<sup>mut</sup> mice. Taken together, these data suggest that G6PD in brown adipocytes would protect against cytosolic oxidative stress, leading to cold-induced thermogenesis.

scholarly journals Complete chloroplast genome of Hordeum brevisubulatum: Genome organization, synonymous codon usage, phylogenetic relationships, and comparative structure analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261196
Author(s):  
Guangxin Cui ◽  
Chunmei Wang ◽  
Xiaoxing Wei ◽  
Hongbo Wang ◽  
Xiaoli Wang ◽  
...  
Keyword(s):  
Phylogenetic Relationships ◽  
Genome Engineering ◽  
De Novo ◽  
Synonymous Codon ◽  
Northern China ◽  
Synonymous Codon Usage ◽  
The Other ◽  
Coding Regions ◽  
Cp Genome ◽  
Hordeum Brevisubulatum

Background Hordeum brevisubulatum, known as fine perennial forage, is used for soil salinity improvement in northern China. Chloroplast (cp) genome is an ideal model for assessing its genome evolution and the phylogenetic relationships. We de novo sequenced and analyzed the cp genome of H. brevisubulatum, providing a fundamental reference for further studies in genetics and molecular breeding. Results The cp genome of H. brevisubulatum was 137,155 bp in length with a typical quadripartite structure. A total of 130 functional genes were annotated and the gene of accD was lost in the process of evolution. Among all the annotated genes, 16 different genes harbored introns and the genes of ycf3 and rps12 contained two introns. Parity rule 2 (PR2) plot analysis showed that majority of genes had a bias toward T over A in the coding strand in all five Hordeum species, and a slight G over C in the other four Hordeum species except for H. bogdanil. Additionally, 52 dispersed repeat sequences and 182 simple sequence repeats were identified. Moreover, some unique SSRs of each species could be used as molecular markers for further study. Compared to the other four Hordeum species, H. brevisubulatum was most closely related to H. bogdanii and its cp genome was relatively conserved. Moreover, inverted repeat regions (IRa and IRb) were less divergent than other parts and coding regions were relatively conserved compared to non-coding regions. Main divergence was presented at the SSC/IR border. Conclusions This research comprehensively describes the architecture of the H. brevisubulatum cp genome and improves our understanding of its cp biology and genetic diversity, which will facilitate biological discoveries and cp genome engineering.

scholarly journals Mosaicism and incomplete penetrance of PCDH19 mutations

2018 ◽  
Vol 56 (2) ◽  
pp. 81-88 ◽  
Author(s):  
Aijie Liu ◽  
Xiaoxu Yang ◽  
Xiaoling Yang ◽  
Qixi Wu ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Male Patient ◽  
Sanger Sequencing ◽  
De Novo ◽  
Digital Pcr ◽  
The Other ◽  
Incomplete Penetrance ◽  
Female Patients ◽  
Targeted Next Generation Sequencing ◽  
Male Patients ◽  
Patients With Epilepsy

BackgroundMutations in the PCDH19 gene have mainly been reported in female patients with epilepsy. To date, PCDH19 mutations have been reported in hundreds of females and only in 10 mosaic male epileptic patients with mosaicism.ObjectiveWe aimed to investigate the occurrence of mosaic PCDH19 mutations in 42 families comprising at least one patient with PCDH19-related epilepsy.MethodsTwo male patients with mosaic PCDH19 variants were identified using targeted next-generation sequencing. Forty female patients with PCDH19 variants were identified by Sanger sequencing and Multiple Ligation Probe Amplification (MLPA). Microdroplet digital PCR was used to quantify the mutant allelic fractions (MAFs) in 20 families with PCDH19 variants.ResultsFive mosaic individuals, four males and one female, were identified in total. Mosaic variant was confirmed in multiple somatic tissues from one male patient and in blood from the other male patient. Among 22 female patients harbouring a newly occurred PCDH19 variant identified by Sanger sequencing and MLPA, Sanger sequencing revealed two mosaic fathers (9%, 2/22), one with two affected daughters and the other with an affected child. Two asymptomatic mosaic fathers were confirmed as gonosomal mosaicism, with MAFs ranging from 4.16% to 37.38% and from 1.27% to 19.13%, respectively. In 11 families with apparent de novo variants, 1 female patient was identified as a mosaic with a blood MAF of 26.72%.ConclusionOur study provides new insights into phenotype-genotype correlations in PCDH19 related epilepsy and the finding of high-frequency mosaicism has important implications for genetic counselling.

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