Branching Pathways Research Articles

The sedoheptulose kinase CARKL controls T cell cytokine outputs and migration by promoting metabolic reprogramming

Abstract Background Immunometabolism is a crucial determinant of immune cell function, influencing cellular activation and differentiation through metabolic pathways. The intricate interplay between metabolism and immune responses is highlighted by the distinct metabolic programs utilized by immune cells to support their functions. Of particular interest is the pentose phosphate pathway (PPP), a key metabolic pathway branching out of glycolysis that plays a pivotal role in generating NADPH and pentose sugars crucial for antioxidant defense and biosynthesis. The sedoheptulose kinase Carbohydrate Kinase-like protein (CARKL), an enzyme involved in the PPP, emerges as a critical regulator of cell metabolism and was previously shown to play a role in macrophage function. Methods This study delves into the impact of CARKL expression on T cell functionality, revealing dynamic alterations in response to cellular activation. Notably, CARKL overexpression leads to significant metabolic shifts in T cells, affecting mitochondrial respiration, ATP production, and inflammatory cytokine profiles. Furthermore, CARKL modulation influences T cell motility by regulating chemokine receptor expression, particularly compromising CXCR3 expression and impairing T cell migration in response to specific chemokine signals. Conclusions These findings underscore the multifaceted role of CARKL as a metabolic regulator shaping T cell responses. Overall, our data reveal the complex regulatory mechanisms orchestrated by CARKL in T cell function, with implications for immune regulation. Further exploration of the molecular interactions between CARKL and metabolic reprogramming in T cells could provide valuable insights into immune regulation and potential therapeutic strategies.

Stage-wise kinetic analysis of ammonia addition effects on two-stage ignition in dimethyl ether

Abstract Ammonia (NH3) has gained considerable attention as a promising carbon-free hydrogen carrier fuel for internal combustion engines, but its direct use in compression-ignition engines presents challenges, often requiring high-reactivity fuels to ignite the premixed NH3/air mixture and initiate combustion. This study focuses on the ignition process of binary NH3 and dimethyl ether (DME) mixtures, as DME is a carbon-neutral, high-reactivity fuel. A key novelty of this paper is the comparison of the ignition processes of DME and NH3/DME mixtures from a temporal, process-oriented perspective, analyzing chemical kinetics across distinct ignition phases rather than focusing solely on instantaneous reactions at discrete time points. The stage-wise analysis reveals that NH3 has minimal impact on the control mechanism governing the two-stage ignition process of DME. Specifically, DME still largely depends on OH radical proliferation during low-temperature oxidation (LTO), which releases heat as the reaction progresses. As the temperature increases, LTO branching pathways gradually shift to chain-propagation pathways, reducing overall reaction activity. The reactivity and temperature rise rate of the system are then governed by the H2O2 loop mechanism before thermal ignition. However, ammonia significantly extends the ignition delay of DME by competing with OH radicals, which are critical for DME oxidation, thus inhibiting ignition. As the ignition reaction proceeds, ammonia kinetics become more involved. For example, nitrogen-containing species from NH3 oxidation, such as NO, NO2, and NH2, react with CH3OCH2 to form CH3OCHO, reducing the flux through the LTO pathway of DME. While ammonia reaction pathways also produce OH radicals, this occurs at the expense of HO2 and H radicals, leading to H2O2 formation. Overall, these findings demonstrate the substantial impact of ammonia addition on DME ignition, highlighting the need for further research to better understand NH3/DME binary fuel ignition and to optimize the design and operation of NH3/DME dual-fuel engines for improved efficiency and reliability.

Ultraviolet Photodissociation Dynamics of the 1-Methylallyl Radical.

The ultraviolet (UV) photodissociation dynamics of the 1-methylallyl (1-MA) radical were studied using the high-n Rydberg atom time-of-flight (HRTOF) technique in the wavelength region of 226-244 nm. The 1-MA radicals were produced by 193 nm photodissociation of the 3-chloro-1-butene and 1-chloro-2-butene precursor. The 1 + 1 REMPI spectrum of 1-MA agrees with the previous UV absorption spectrum in this wavelength region. Quantum chemistry calculations show that the UV absorption is mainly attributed to the 3pz Rydberg state (perpendicular to the allyl plane). The H atom photofragment yield (PFY) spectrum of 1-MA from 3-chloro-1-butene displays a broad peak around 230 nm, while that from 1-chloro-2-butene peaks at ∼236 nm. The translational energy distributions of the H atom loss product channel, P (ET)'s, show a bimodal distribution indicating two dissociation pathways in 1-MA. The major pathway is isotropic in product angular distribution with β ∼ 0 and has a low fraction of average translational energy in the total excess energy, ⟨fT⟩, in the range of 0.13-0.17; this pathway corresponds to unimolecular dissociation of 1-MA after internal conversion to form 1,3-butadiene + H. The minor pathway is anisotropic with β ∼ -0.23 and has a large ⟨fT⟩ of ∼0.62-0.72. This fast pathway suggests a direct dissociation of the methyl H atom on a repulsive excited state surface or the repulsive part of the ground state surface to form 1,3-butadiene + H. The fast/slow pathway branching ratio is in the range of 0.03-0.08.

Glucose metabolism in B cell malignancies: a focus on glycolysis branching pathways.

Glucose catabolism, one of the essential pathways sustaining cellular bioenergetics, has been widely studied in the context of tumors. Nevertheless, the function of various branches of glucose metabolism that stem from 'classical' glycolysis have only been partially explored. This review focuses on discussing general mechanisms and pathological implications of glycolysis and its branching pathways in the biology of B cell malignancies. We summarize here what is known regarding pentose phosphate, hexosamine, serine biosynthesis, and glycogen synthesis pathways in this group of tumors. Despite most findings have been based on malignant B cells themselves, we also discuss the role of glucose metabolism in the tumor microenvironment, with a focus on T cells. Understanding the contribution of glycolysis branching pathways and how they are hijacked in B cell malignancies will help to dissect the role they have in sustaining the dissemination and proliferation of tumor B cells and regulating immune responses within these tumors. Ultimately, this should lead to deciphering associated vulnerabilities and improve current therapeutic schedules.

Time-resolved quantification of key species and mechanistic insights in low-temperature tetrahydrofuran oxidation.

We investigate the kinetics and report the time-resolved concentrations of key chemical species in the oxidation of tetrahydrofuran (THF) at 7500 torr and 450-675 K. Experiments are carried out using high-pressure multiplexed photoionization mass spectrometry (MPIMS) combined with tunable vacuum ultraviolet radiation from the Berkely Lab Advanced Light Source. Intermediates and products are quantified using reference photoionization (PI) cross sections, when available, and constrained by a global carbon balance tracking approach at all experimental temperatures simultaneously for the species without reference cross sections. From carbon balancing, we determine time-resolved concentrations for the ROO˙ and ˙OOQOOH radical intermediates, butanedial, and the combined concentration of ketohydroperoxide (KHP) and unsaturated hydroperoxide (UHP) products stemming from the ˙QOOH + O2 reaction. Furthermore, we quantify a product that we tentatively assign as fumaraldehyde, which arises from UHP decomposition via H2O or ˙OH + H loss. The experimentally derived species concentrations are compared with model predictions using the most recent literature THF oxidation mechanism of Fenard et al., (Combust. Flame, 2018, 191, 252-269). Our results indicate that the literature mechanism significantly overestimates THF consumption and the UHP + KHP concentration at our conditions. The model predictions are sensitive to the rate coefficient for the ROO˙ isomerization to ˙QOOH, which is the gateway for radical chain propagating and branching pathways. Comparisons with our recent results for cyclopentane (Demireva et al., Combust. Flame, 2023, 257, 112506) provide insights into the effect of the ether group on reactivity and highlight the need to determine accurate rate coefficients of ROO˙ isomerization and subsequent reactions.

Excited state dynamics of homoleptic Zn(ii)dipyrrin complexes and their application in photocatalysis

Using Zn-dipyrrins as photocatalysts involves exciting an intramolecular charge-transfer (ICT) state and intersystem crossing (ISC). To optimize the catalyst, studying ISC branching pathways competing with fluorescence and internal conversion (IC) is essential.

Ultraviolet photochemistry of the 2-buten-2-yl radical.

The ultraviolet (UV) photodissociation dynamics of the 2-buten-2-yl (C4H7) radical were studied using the high-n Rydberg atom time-of-flight (HRTOF) technique in the photolysis region of 226-246 nm. 2-Buten-2-yl radicals were generated by 193 nm photodissociation of the precursor 2-chloro-2-butene. The H-atom photofragment yield (PFY) spectrum of 2-buten-2-yl is broad, peaking at 234 nm. Quantum chemistry calculations show that the UV absorption is due to the 3py and 3px Rydberg states (parallel to the plane of CC double bond). The translational energy distributions of the H-atom loss product channel, P(ET)'s, of 2-buten-2-yl show a bimodal distribution indicating two dissociation pathways. The major pathway peaks at ET ∼ 7 kcal mol-1 with a nearly constant fraction of average ET in the total excess energy, 〈fT〉, at ∼0.11-0.12. This main pathway has an isotropic product angular distribution with β ∼ 0, consistent with the unimolecular dissociation of a hot 2-buten-2-yl radical following internal conversion from the electronically excited state, resulting in the formation of 2-butyne + H (∼84%) and 1,2-butadiene + H (∼16%). Additionally, there is a minor non-statistical pathway with an isotropic angular distribution. The minor pathway peaks at ET ∼ 35 kcal mol-1 in the P(ET) distributions and exhibits a large 〈fT〉 of ∼0.40-0.46. This fast pathway suggests a direct dissociation of the methyl H-atom on a repulsive excited state surface or on the repulsive part of the ground state surface, forming 1,2-butadiene + H. The fast/slow pathway branching ratio is in the range of 0.03-0.08.

Optimization of trans-4-hydroxyproline synthesis pathway by rearrangement center carbon metabolism in Escherichia coli

Backgroundtrans-4-Hydroxyproline (T-4-HYP) is a promising intermediate in the synthesis of antibiotic drugs. However, its industrial production remains challenging due to the low production efficiency of T-4-HYP. This study focused on designing the key nodes of anabolic pathway to enhance carbon flux and minimize carbon loss, thereby maximizing the production potential of microbial cell factories.ResultsFirst, a basic strain, HYP-1, was developed by releasing feedback inhibitors and expressing heterologous genes for the production of trans-4-hydroxyproline. Subsequently, the biosynthetic pathway was strengthened while branching pathways were disrupted, resulting in increased metabolic flow of α-ketoglutarate in the Tricarboxylic acid cycle. The introduction of the NOG (non-oxidative glycolysis) pathway rearranged the central carbon metabolism, redirecting glucose towards acetyl-CoA. Furthermore, the supply of NADPH was enhanced to improve the acid production capacity of the strain. Finally, the fermentation process of T-4-HYP was optimized using a continuous feeding method. The rate of sugar supplementation controlled the dissolved oxygen concentrations during fermentation, and Fe2+ was continuously fed to supplement the reduced iron for hydroxylation. These modifications ensured an effective supply of proline hydroxylase cofactors (O2 and Fe2+), enabling efficient production of T-4-HYP in the microbial cell factory system. The strain HYP-10 produced 89.4 g/L of T-4-HYP in a 5 L fermenter, with a total yield of 0.34 g/g, the highest values reported by microbial fermentation, the yield increased by 63.1% compared with the highest existing reported yield.ConclusionThis study presents a strategy for establishing a microbial cell factory capable of producing T-4-HYP at high levels, making it suitable for large-scale industrial production. Additionally, this study provides valuable insights into regulating synthesis of other compounds with α-ketoglutaric acid as precursor.

Social Stratification, Genealogical Distance, and State Formation in Early Hawaii and the Central Andes: Steps, Slopes, and Off-Ramps in Social Evolution

Henri J. M. Claessen proposed that the early state came into being by a process of social stratification that led to the creation of genealogical distance between a ruler and the ruled. This article evaluates Claessen's proposition by comparing the development of early large-scale polities in Hawaii and the central Andes. The process of state formation in Hawaii largely followed Claessen's proposed ‘slope’ of political development – by the end of the sequence, kings were seen as gods in the protohistoric Hawaiian state. The central Andean Wari polity, in contrast, took an ‘off-ramp’ from Claessen's slope to a more heterarchical political structure of competing elite-led corporate groups. We explain some of the possible reasons for the differences between our case studies and emphasize that there are many branching pathways to greater political complexity in the ancient world.

Highly efficient production of ectoine via an optimized combination of precursor metabolic modules in Escherichia coli BL21

Ectoine is an osmotic pressure protectant observed in various microorganisms and is widely used in cosmetics and pharmaceuticals. The market value of ectoine has increased considerably with social progress, resulting in high demand for ectoine production technology. Herein, a microbial cell factory in Escherichia coli that produces ectoine at high titers is described as developing efficient and environmentally friendly bio-based ectoine production technology. The ectoine biosynthetic pathway of Halomonas hydrothermalis was introduced into E. coli BL21 (DE3). Subsequent overexpression of precursor metabolic modules, including aspartate branching, pyruvate-oxoacetate, and glutamate biosynthesis pathways, resulted in the final strain, E. coli BCT08, which produced ectoine at a titer of 36.58 g/L during 30 h of fermentation. Sugar feeding speed optimization improved the ectoine titer to 131.8 g/L after 96 h of cultivation. This represents a remarkable achievement in ectoine production from glucose under low-salt conditions and has vast potential for industrial applications.

Three-dimensional neutron far-field tomography of a bulk skyrmion lattice

AbstractMagnetic skyrmions are localized non-collinear spin textures, characterized by an integer topological charge. Commonly observed in thin systems as two-dimensional sheets, in three dimensions skyrmions form tubes that are thought to nucleate and annihilate along their depth on points of vanishing magnetization. However, a lack of techniques that can probe the bulk of the material has made it difficult to perform experimental visualizations of skyrmion lattices and their stabilization through defects. Here we present three-dimensional visualizations of a bulk Co8Zn8Mn4 skyrmion lattice through a tomographic algorithm applied to multiprojection small-angle neutron scattering measurements. Reconstructions of the sample show a disordered skyrmion lattice exhibiting three-dimensional topological transitions through emergent (anti)monopole branching and segmentation defect pathways. Our technique provides insights into skyrmion stabilization and topological transition pathways in a bulk skyrmion lattice, guiding the future development and manipulation of skyrmion materials for spintronic applications.

The Gene paaZ of the Phenylacetic Acid (PAA) Catabolic Pathway Branching Point and ech outside the PAA Catabolon Gene Cluster Are Synergistically Involved in the Biosynthesis of the Iron Scavenger 7-Hydroxytropolone in Pseudomonas donghuensis HYS.

The newly discovered iron scavenger 7-hydroxytropolone (7-HT) is secreted by Pseudomonas donghuensis HYS. In addition to possessing an iron-chelating ability, 7-HT has various other biological activities. However, 7-HT's biosynthetic pathway remains unclear. This study was the first to report that the phenylacetic acid (PAA) catabolon genes in cluster 2 are involved in the biosynthesis of 7-HT and that two genes, paaZ (orf13) and ech, are synergistically involved in the biosynthesis of 7-HT in P. donghuensis HYS. Firstly, gene knockout and a sole carbon experiment indicated that the genes orf17-21 (paaEDCBA) and orf26 (paaG) were involved in the biosynthesis of 7-HT and participated in the PAA catabolon pathway in P. donghuensis HYS; these genes were arranged in gene cluster 2 in P. donghuensis HYS. Interestingly, ORF13 was a homologous protein of PaaZ, but orf13 (paaZ) was not essential for the biosynthesis of 7-HT in P. donghuensis HYS. A genome-wide BLASTP search, including gene knockout, complemented assays, and site mutation, showed that the gene ech homologous to the ECH domain of orf13 (paaZ) is essential for the biosynthesis of 7-HT. Three key conserved residues of ech (Asp39, His44, and Gly62) were identified in P. donghuensis HYS. Furthermore, orf13 (paaZ) could not complement the role of ech in the production of 7-HT, and the single carbon experiment indicated that paaZ mainly participates in PAA catabolism. Overall, this study reveals a natural association between PAA catabolon and the biosynthesis of 7-HT in P. donghuensis HYS. These two genes have a synergistic effect and different functions: paaZ is mainly involved in the degradation of PAA, while ech is mainly related to the biosynthesis of 7-HT in P. donghuensis HYS. These findings complement our understanding of the mechanism of the biosynthesis of 7-HT in the genus Pseudomonas.

Surgical anatomy of the dorsal pancreatic artery: Considering embryonic development

ObjectivesThe dorsal pancreatic artery (DPA) is a pancreatic branch with various anatomical variations. Previous studies mostly focused on the origin of the DPA, and its pathways and branching patterns have rarely been examined. The purpose of this study was to investigate the branching patterns and pathways of the DPA. MethodsThis study included 110 patients who underwent computed tomography scans. We examined the pathways and branching patterns of the DPA. ResultsThe DPA was identified in 101 patients (92%), and originated from the splenic artery in 30 patients (31%), the common hepatic artery in 17 patients (17%), the celiac trunk in 10 patients (10%), the superior mesenteric artery in 27 patients (27%), the replaced right hepatic artery in 7 patients (7%), the inferior pancreaticoduodenal artery in 5 patients (5%), and other arteries in 3 patients (3%). Four distinct types of branches were identified as follows: the superior branch (32%), the inferior branch (86%), the right branch (80%), and the accessory middle colic artery (12%). Additionally, the arcs of Buhler and Riolan were observed in two patients each and their anastomotic vessels followed almost the same pathway as the DPA. ConclusionA number of variations of the DPA were observed with regard to its origin and branching pattern; however, the DPA and its branches always ran along the same pathway, as summarized in Fig. 4. The anatomical information gained from this study may contribute to performing safe pancreatic resections.

Characterization of metabolic reprogramming by metabolomics in the oncocytic thyroid cancer cell line XTC.UC1

Oncocytic thyroid cancer is characterized by the aberrant accumulation of abnormal mitochondria in the cytoplasm and a defect in oxidative phosphorylation. We performed metabolomics analysis to compare metabolic reprogramming among the oncocytic and non-oncocytic thyroid cancer cell lines XTC.UC1 and TPC1, respectively, and a normal thyroid cell line Nthy-ori 3-1. We found that although XTC.UC1 cells exhibit higher glucose uptake than TPC1 cells, the glycolytic intermediates are not only utilized to generate end-products of glycolysis, but also diverted to branching pathways such as lipid metabolism and the serine synthesis pathway. Glutamine is preferentially used to produce glutathione to reduce oxidative stress in XTC.UC1 cells, rather than to generate α-ketoglutarate for anaplerotic flux into the TCA cycle. Thus, growth, survival and redox homeostasis of XTC.UC1 cells rely more on both glucose and glutamine than do TPC1 cells. Furthermore, XTC.UC1 cells contained higher amounts of intracellular amino acids which is due to higher expression of the amino acid transporter ASCT2 and enhanced autophagy, thus providing the building blocks for macromolecules and energy production. These metabolic alterations are required for oncocytic cancer cells to compensate their defective mitochondrial function and to alleviate excess oxidative stress.

Counterflow flame extinction of ammonia and its blends with hydrogen and C1-C3 hydrocarbons

Ammonia as a fuel offers the potential to avoid carbon emissions, but its combustion is hindered by low reactivity. Here, the extinction limits of NH3 and NH3 plus reactivity enhancers were measured in the counterflow laminar non-premixed flames. A stable NH3-N2 flame was established with an oxygen-enriched oxidizer stream, and when the fuel was blended with CH4, C2H6, C3H8, and H2. For blended mixtures, results showed that CH4 has the least potential to enhance the stability of NH3 flames compared to the other additives. The extinction limits of C2H6 and C3H8 blended NH3 flames are nearly identical. At low percentage addition, H2-blended flames extinguish earlier than those blended with C1-C3 hydrocarbons, but this trend is reversed at higher H2 blends. Experimental conditions were simulated using Okafor et al. 2018 model and an extended Zhang et al 2021 model developed here. The models captured the measured trends, including the crossover between NH3-H2 and NH3-C2/C3 hydrocarbon fuels. Quantitatively, both models under-predicted the extinction limits of NH3-N2/enriched oxidizer flame. Better quantitative agreement is observed for the blended fuels using the model developed here. Discrepancies have been observed in the reported rates for reactions involving HNO (+OH, H), and if addressed, could improve models' capability in predicting extinction behavior in non-premixed flames. Numerical analyses were carried out to understand the kinetic coupling between NH3 and H2/C2-C3 in counter-flow flames. Extinction limits of NH3-C2-C3/H2 flames are shown to be affected by H abstraction and NH3 related chain termination reactions, heat producing reactions, and chain branching reactions. It has also been observed that at high blending ratios, C2H6/C3H8 addition in NH3 flames reduced the peak H and OH concentration via recombination and termination reactions, which compete with branching pathways. H2-blended flames are mostly influenced by reactions producing active radicals.

Biosynthetic Elucidation and Structural Revision of Brevione E: Characterization of the Key Dioxygenase for Pathway Branching from Setosusin Biosynthesis.

Brevione E (1) is a fungal hexacyclic meroditerpenoid with unique oxepane and cycloheptenone moieties. In this study, we identified the biosynthetic gene cluster of 1 and elucidated its biosynthetic pathway via heterologous expression of the biosynthetic genes and in vitro enzymatic reactions. Surprisingly, reexamination of the structure of 1 revealed a substituted tetrahydrofuran ring instead of the previously proposed oxepane system. Moreover, we determined that cycloheptenone synthesis involves skeletal rearrangement catalyzed by the α-ketoglutarate-dependent dioxygenase BrvJ. BrvJ is highly homologous to SetK, which engages in the biosynthesis of another fungal metabolite, setosusin, and accepts the same substrate as BrvJ but performs only simple hydroxylation. Finally, we identified the key amino acid residues critical for product selectivity of BrvJ and SetK, providing insight into how the biosynthesis pathways of 1 and setosusin diverge and how fungi diversify natural products.

Biosynthetic Elucidation and Structural Revision of Brevione E: Characterization of the Key Dioxygenase for Pathway Branching from Setosusin Biosynthesis

Brevione E (1) is a fungal hexacyclic meroditerpenoid with unique oxepane and cycloheptenone moieties. In this study, we identified the biosynthetic gene cluster of 1 and elucidated its biosynthetic pathway via heterologous expression of the biosynthetic genes and in vitro enzymatic reactions. Surprisingly, reexamination of the structure of 1 revealed a substituted tetrahydrofuran ring instead of the previously proposed oxepane system. Moreover, we determined that cycloheptenone synthesis involves skeletal rearrangement catalyzed by the α-ketoglutarate-dependent dioxygenase BrvJ. BrvJ is highly homologous to SetK, which engages in the biosynthesis of another fungal metabolite, setosusin, and accepts the same substrate as BrvJ but performs only simple hydroxylation. Finally, we identified the key amino acid residues critical for product selectivity of BrvJ and SetK, providing insight into how the biosynthesis pathways of 1 and setosusin diverge and how fungi diversify natural products.

Evaluating the role of hydroxyl keto-hydroperoxide in the low temperature oxidation of alkenes

The low temperature oxidation of alkenes exhibits some distinct reaction pathways that may form different kinds of keto-hydroperoxides to start the chain-branching by further decomposition. This is mainly due to the existence of the double bond that the OH radical could add to it. This work explores that phenomenon by investigating the low temperature oxidation of three alkenes (1-hexene, 1-heptene and 1-decene) in a jet-stirred reactor (JSR) at atmospheric pressure. The synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS) experiments combined with hydrogen-deuterium (H-D) exchange reactions were used to evaluate the chain branching pathways. Alkenyl keto-hydroperoxide (AnKHP) and hydroxyl keto-hydroperoxide (HyKHP) are identified. They represented two different chain branching reaction networks that are initiated from the H-abstraction of the primary and secondary CHs and via OH addition to the double bond. The experimental estimated and model predicted ratios of AnKHP to HyKHP are compared, and the result indicates that the literature model underpredicts the chain branching reactions via the formation of AnKHP, but overpredicts the chain branching reactions via HyKHP.

Aurora A–mediated pyruvate kinase M2 phosphorylation promotes biosynthesis with glycolytic metabolites and tumor cell cycle progression

Cancer cells have distinctive demands for intermediates from glucose metabolism for biosynthesis and energy in different cell cycle phases. However, how cell cycle regulators and glycolytic enzymes coordinate to orchestrate the essential metabolic processes are still poorly characterized. Here, we report a novel interaction between the mitotic kinase, Aurora A, and the glycolytic enzyme, pyruvate kinase M2 (PKM2), in the interphase of the cell cycle. We found Aurora A-mediated phosphorylation of PKM2 at threonine 45. This phosphorylation significantly attenuated PKM2 enzymatic activity by reducing its tetramerization and also promoted glycolytic flux and the branching anabolic pathways. Replacing the endogenous PKM2 with a nonphosphorylated PKM2 T45A mutant inhibited glycolysis, glycolytic branching pathways, and tumor growth in both invitro and invivo models. Together, our study revealed a new protumor function of Aurora A through modulating a rate-limiting glycolytic enzyme, PKM2, mainly during the S phase of the cell cycle. Our findings also showed that although both Aurora A and Aurora B kinase phosphorylate PKM2 at the same residue, the spatial and temporal regulations of the specific kinase and PKM2 interaction are context dependent, indicating intricate interconnectivity between cell cycle and glycolytic regulators.

Experimental and Modeling Evaluation of Dimethoxymethane as an Additive for High-Pressure Acetylene Oxidation.

The high-pressure oxidation of acetylene–dimethoxymethane (C2H2–DMM) mixtures in a tubular flow reactor has been analyzed from both experimental and modeling perspectives. In addition to pressure (20, 40, and 60 bar), the influence of the oxygen availability (by modifying the air excess ratio, λ) and the presence of DMM (two different concentrations have been tested, 70 and 280 ppm, for a given concentration of C2H2 of 700 ppm) have also been analyzed. The chemical kinetic mechanism, progressively built by our research group in the last years, has been updated with recent theoretical calculations for DMM and validated against the present results and literature data. Results indicate that, under fuel-lean conditions, adding DMM enhances C2H2 reactivity by increased radical production through DMM chain branching pathways, more evident for the higher concentration of DMM. H-abstraction reactions with OH radicals as the main abstracting species to form dimethoxymethyl (CH3OCHOCH3) and methoxymethoxymethyl (CH3OCH2OCH2) radicals are the main DMM consumption routes, with the first one being slightly favored. There is a competition between β-scission and O2-addition reactions in the consumption of both radicals that depends on the oxygen availability. As the O2 concentration in the reactant mixture is increased, the O2-addition reactions become more relevant. The effect of the addition of several oxygenates, such as ethanol, dimethyl ether (DME), or DMM, on C2H2 high-pressure oxidation has been compared. Results indicate that ethanol has almost no effect, whereas the addition of an ether, DME or DMM, shifts the conversion of C2H2 to lower temperatures.