Enhanced Catalytic Activity of Boron Nitride Nanotubes by Encapsulation of Nickel Wire Toward O2 Activation and CO Oxidation: A Theoretical Study

Perfect boron nitride (BN) nanotubes are chemically inert, and hardly considered as catalysts. Nevertheless, metal wire encapsulated BN nanotubes show extraordinarily high chemical activity. We report nickel (Ni) nanowire encapsulated BN(8.0) and BN(9.0) nanotubes toward O2 activation and CO oxidization on the basis of first-principles calculations. Our results suggest that Ni wire encapsulated BN(8.0) and BN(9.0) nanotubes can easily adsorb and activate O2 molecules to form peroxo or superoxo species exothermically. Meanwhile, superoxo species are ready to react with CO molecules forming OCOO intermediate state and finally yielding CO2 molecules. Meanwhile, the rate-limiting step barrier is only 0.637 eV, implying excellent performance for CO oxidation on Ni nanowire encapsulated BN nanotubes. Furthermore, encapsulation of nickel wire improves the catalytic activity of BN nanotubes by facilitating electron transfer from Ni wire to BN nanotubes, which facilitates the adsorption of highly electronegative O2 molecules and subsequent CO oxidation. This study provides a practical and efficient strategy for activating O2 on a metal encapsulated BN nanotube toward CO oxidation.

Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation

Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by catecholamines and reactivation by S40 phosphorylation are key regulatory mechanisms of TH activity and conformational stability. We used Cryo-EM to determine the structures of full-length human TH without and with DA, and the structure of S40 phosphorylated TH, complemented with biophysical and biochemical characterizations and molecular dynamics simulations. TH presents a tetrameric structure with dimerized regulatory domains that are separated 15 Å from the catalytic domains. Upon DA binding, a 20-residue α-helix in the flexible N-terminal tail of the regulatory domain is fixed in the active site, blocking it, while S40-phosphorylation forces its egress. The structures reveal the molecular basis of the inhibitory and stabilizing effects of DA and its counteraction by S40-phosphorylation, key regulatory mechanisms for homeostasis of DA and TH.

Soils and sediments host Thermoplasmata archaea encoding novel copper membrane monooxygenases (CuMMOs)

Copper membrane monooxygenases (CuMMOs) play critical roles in the global carbon and nitrogen cycles. Organisms harboring these enzymes perform the first, and rate limiting, step in aerobic oxidation of ammonia, methane, or other simple hydrocarbons. Within archaea, only organisms in the order Nitrososphaerales (Thaumarchaeota) encode CuMMOs, which function exclusively as ammonia monooxygenases. From grassland and hillslope soils and aquifer sediments, we identified 20 genomes from distinct archaeal species encoding divergent CuMMO sequences. These archaea are phylogenetically clustered in a previously unnamed Thermoplasmatota order, herein named the Ca. Angelarchaeales. The CuMMO proteins in Ca. Angelarchaeales are more similar in structure to those in Nitrososphaerales than those of bacteria, and contain all functional residues required for general monooxygenase activity. Ca. Angelarchaeales genomes are significantly enriched in blue copper proteins (BCPs) relative to sibling lineages, including plastocyanin-like electron carriers and divergent nitrite reductase-like (nirK) 2-domain cupredoxin proteins co-located with electron transport machinery. Ca. Angelarchaeales also encode significant capacity for peptide/amino acid uptake and degradation and share numerous electron transport mechanisms with the Nitrososphaerales. Ca. Angelarchaeales are detected at high relative abundance in some of the environments where their genomes originated from. While the exact substrate specificities of the novel CuMMOs identified here have yet to be determined, activity on ammonia is possible given their metabolic and ecological context. The identification of an archaeal CuMMO outside of the Nitrososphaerales significantly expands the known diversity of CuMMO enzymes in archaea and suggests previously unaccounted organisms contribute to critical global nitrogen and/or carbon cycling functions.

A review on nirS-type and nirK-type denitrifiers via a scientometric approach coupled with case studies

The denitrification process plays an important role in improving water quality and is a source/sink of nitrous oxide to the atmosphere. The second important rate-limiting step of denitrification process is...

eIF4A2 targets developmental potency and histone H3.3 transcripts for translational control of stem cell pluripotency

Translational control has emerged as a fundamental regulatory layer of proteome complexity that governs cellular identity and functions. As initiation is the rate-limiting step of translation, we carried out an RNAi screen for key translation initiation factors required to maintain embryonic stem cell (ESC) identity. We identified eIF4A2 and defined its mechanistic action through Rps26-independent and -dependent ribosomes in translation initiation activation of mRNAs encoding pluripotency factors and the histone variant H3.3 with demonstrated roles in maintaining stem cell pluripotency. eIF4A2 also mediates translation initiation activation of Ddx6, which acts together with eIF4A2 to restrict the totipotent 2-cell transcription program in ESCs through Zscan4 mRNA degradation and translation repression. Accordingly, knockdown of eIF4A2 disrupts ESC proteome causing the loss of ESC identity. Collectively, we establish a translational paradigm of the protein synthesis of pluripotency transcription factors and epigenetic regulators imposed on their established roles in controlling pluripotency.

Cyp11a2 is essential for oocyte development and spermatogonial stem cell differentiation in zebrafish

Cytochrome P45011A1, encoded by Cyp11a1, converts cholesterol to pregnenolone (P5), the first and rate-limiting step in steroidogenesis. In zebrafish, cyp11a1 is maternally expressed and cyp11a2 is considered the ortholog of Cyp11a1 in mammals. A recent study has shown that depletion of cyp11a2 resulted in steroidogenic deficiencies and the mutants developed into males with feminized secondary sexual characteristics. Here, we independently generated cyp11a2 mutants in zebrafish and showed that the mutants can develop into males and females in the juvenile stage, but finally into infertile males with defective mating behavior in the adult stage. In the developing ovaries, the cyp11a2 mutation led to stage I oocyte apoptosis and final sex reversal, which could be partially rescued by treatment with P5 but not estradiol. In the developing testes, depletion of cyp11a2 resulted in dysfunction of Sertoli cells and lack of functional Leydig cells. Spermatogonial stem cells (SSCs) in the mutant testes underwent active self-renewal but no differentiation, resulting in a high abundance of SSCs in the testis, as revealed by immunofluorescence staining with Nanos2 antibody. The high abundance and differentiation competence of SSCs in the mutant testes were verified by a novel testicular cell transplantation (TCT) method developed in this study, by transplanting mutant testicular cells into germline-depleted wild-type (WT) fish. The transplanted mutant SSCs efficiently differentiated into functional spermatids in WT hosts. Overall, our study demonstrates the functional importance of cyp11a2 in early oogenesis and differentiation of SSCs.

Capillary Endothelial Insulin Transport: The Rate Limiting Step for Insulin-stimulated Glucose Uptake

The rate limiting step for skeletal muscle glucose uptake is transport from microcirculation to muscle interstitium. Capillary endothelium poses a barrier that delays the onset of muscle insulin action. Defining physiological barriers that control insulin access to interstitial space is difficult due to technical challenges that confront study of microscopic events in an integrated physiological system. Two physiological variables determine muscle insulin access. These are the number of perfused capillaries and the permeability of capillary walls to insulin. Disease states associated with capillary rarefaction are closely linked to insulin resistance. Insulin permeability through high resistant capillary walls of muscle poses a significant barrier to insulin access. Insulin may traverse the endothelium through narrow intercellular junctions or vesicular trafficking across the endothelial cell. Insulin is large compared to intercellular junctions making this an unlikely route. Transport by endothelial vesicular trafficking is likely the primary route of transit. Studies in vivo show movement of insulin is not insulin receptor-dependent. This aligns with single cell transcriptomics that show the insulin receptor is not expressed in muscle capillaries. Work in cultured endothelial cell lines suggest that insulin receptor activation is necessary for endothelial insulin transit. Controversies remain in the understanding of trans-endothelial insulin transit to muscle. These controversies closely align with experimental approaches. Control of circulating insulin accessibility to skeletal muscle is an area that remains ripe for discovery. Factors that impede insulin access to muscle may contribute to disease and factors that accelerate access may be of therapeutic value for insulin resistance.

Considerations on the kinetic correlation between SiC nitridation and etching at the 4H-SiC(0001)/SiO2 interface in N2 and N2/H2 ambient

Kinetics of SiC surface nitridation process of high-temperature N2 annealing was investigated with 4H-SiC(0001)/SiO2 structure based on the correlation between the rates of N incorporation and SiC consumption induced by SiC etching. During the early stage of the annealing process, the rate-limiting step for N incorporation would be the removal of the topmost C atoms in the slow-etching case, while it would be another reaction step, probably the activation process of nitrogen in the fast-etching case. The SiO2 layer thickness and the annealing ambient which serve as the parameters to affect the SiC etching rate, would determine the N incorporation rate according to the kinetic correlation between the N incorporation and SiC etching. The SiC consumption observed during high-temperature annealing in N2 or N2/H2 ambient would be induced by the active oxidation by residual O2 or H2O in the ambient, which would lead to the SiC surface roughening.

Calculation of the Tafel slope and reaction order of the oxygen evolution reaction between pH 12 and pH 14 for the adsorbate mechanism

Despite numerous experimental and theoretical studies devoted to the oxygen evolution reaction, the mechanism of the OER on transition metal oxides remains controversial. This is in part owed to the ambiguity of electrochemical parameters of the mechanism such as the Tafel slope and reaction orders. We took the most commonly assumed adsorbate mechanism and calculated the Tafel slopes and reaction orders with respect to pH based on microkinetic analysis. We demonstrate that number of possible Tafel slopes strongly depends on a number of preceding steps and surface coverage. Furthermore, the Tafel slope becomes pH dependent when the coverage of intermediates changes with pH. These insights complicate the identification of a rate-limiting step by a single Tafel slope at a single pH. Yet, simulations of reaction orders complementary to Tafel slopes can solve some ambiguities to distinguish between possible rate-limiting steps. The most insightful information can be obtained from the low overpotential region of the Tafel plot. The simulations in this work provide clear guidelines to experimentalists for the identification of the limiting steps in the adsorbate mechanism using the observed values of the Tafel slope and reaction order in pH-dependent studies.

Revealing a hidden intermediate of rotatory catalysis with X-ray crystallography and Molecular simulations

The mechanism of rotatory catalysis in ATP-hydrolyzing molecular motors remain an unresolved puzzle in biological energy transfer. Notwithstanding the wealth of available biochemical and structural information inferred from years of experiments, knowledge on how the coupling between the chemical and mechanical steps within motors enforces directional rotatory movements remains fragmentary. Even more contentious is to pinpoint the rate-limiting step of a multi-step rotation process. Here, using Vacuolar or V1-type hexameric ATPase as an exemplary rotational motor, we present a model of the complete 4-step conformational cycle involved in rotatory catalysis. First, using X-ray crystallography a new intermediate or 'dwell' is identified, which enables the release of an inorganic phosphate (or Pi) after ATP hydrolysis. Using molecular dynamics simulations, this new dwell is placed in a sequence with three other crystal structures to derive a putative cyclic rotation path. Free-energy simulations are employed to estimate the rate of the hexameric protein transfor-mations, and delineate allosteric effects that allow new reactant ATP entry only after hydrolysis product exit. An analysis of transfer entropy brings to light how the sidechain level interactions transcend into larger scale reorganizations, highlighting the role of the ubiquitous arginine-finger residues in coupling chemical and mechanical information. Inspection of all known rates encompassing the 4-step rotation mechanism implicates overcoming of the ADP interactions with V1-ATPase to be the rate-limiting step of motor action.