Acid Research Articles

Acid Catalysis Mediated by Aqueous Hydronium Ions Formed by Contacting Zeolite Crystals with Liquid Water.

Zeolites are crystalline microporous aluminosilicates widely used as solid acids in catalytic routes to clean and sustainable energy carriers and chemicals from biogenic and fossil feedstocks. This study addresses how zeolites act as weak polyprotic acids and dissociate to form extra-crystalline hydronium (H3O+) ions in liquid water. The extent of their dissociation depends on the energy required to form the conjugate framework anions, which becomes unfavorable as the extent of dissociation increases intracrystalline charge densities because repulsive interactions ultimately preclude the detachment of all protons as catalytically relevant H3O+(aq) ions. The extent of dissociation is accurately described using electrostatic repulsion formalisms that account for aqueous H3O+ concentrations for all zeolite concentrations, Al densities, and frameworks. Probed by hydrolysis of cellulose, the most abundant biogenic polymer, this study demonstrates that zeolites catalyze this reaction exclusively through the formation of the extra-crystalline H3O+ ions at rates strictly proportional to their concentrations in the aqueous phase, irrespective of their provenance from zeolites differing in framework structure or Al content, without the purported involvement of acid sites at extracrystalline surfaces or intervening formation of smaller cellulose oligomers. The results and mechanistic interpretations seamlessly and rigorously bridge the chemistry of solid and liquid acids in aqueous media, while resolving the enduring puzzle of solid acids that catalyze transformations of substrates that cannot enter the voids where acid sites reside.

Electrophilic Intermediates in the Nef and Meyer Reactions: A Computational Study.

The generation, interconversion, and reactivity of electrophilic species generated upon activation of nitroalkanes with protic acids (the Nef and Meyer reactions) were investigated by quantum-chemical calculations. N,N-Bis(hydroxy)iminium (R2C═N+(OH)2) and N-oxoiminium (R2C═N+═O) cations were shown to be produced independently from aci-nitroalkanes, while N-hydroxynitrilium cations (RC≡N+-OH) were formed via nearly barrierless C-H bond cleavage in N-oxoiminium cations. The N-oxoiminium and N-hydroxynitrilium cations whose formation is favored under highly acidic anhydrous conditions are strong electrophiles capable of reacting even with nonactivated arenes under ambient conditions. The N-oxoiminium cations R2C═N+═O are highly unusual ambident species containing three contiguous electrophilic centers (C, N, and O atoms). Nucleophilic addition at the oxygen atom is less preferred than the C- and N-attack yet possible in an intramolecular variant. These computational results shed light on some key aspects of the mechanisms of the Nef and Meyer reactions and predict the possibility of numerous interrupted versions of these reactions.

Site-Specific Immobilization Boosts the Performance of a Galectin-1 Biosensor.

The analysis of protein-bound glycans has gained significant attention due to their pivotal roles in physiological and pathological processes like cell-cell recognition, immune response, and disease progression. Routine methods for glycan analysis are challenged by the very similar physicochemical properties of their carbohydrate components. As an alternative, lectins, which are proteins that specifically bind to glycans, have been integrated into biosensors for glycan detection. However, the effectiveness of protein-based biosensors depends heavily on the immobilization of proteins on the sensor surface. To enhance the sensitivity and/or selectivity of lectin biosensors, it is crucial to immobilize the lectin in an optimal orientation for ligand binding without compromising its function. Random immobilization methods often result in arbitrary orientation and reduced sensitivity. To address this, we explored a directed immobilization strategy relying on a reactive noncanonical amino acid (ncAA) and bioorthogonal chemistry. In this study, we site-specifically incorporated the reactive noncanonical lysine derivative, Nε-((2-azidoethoxy)carbonyl)-l-lysine, into a cysteine-less single-chain variant of human galectin-1 (scCSGal-1). The reactive bioorthogonal azide group allowed the directed immobilization of the lectin on a biosensor surface using strain-promoted azide-alkyne cycloaddition. Biolayer interferometry data demonstrated that the controlled, directed attachment of scCSGal-1 to the biosensor surface enhanced the binding sensitivity to glycosylated von Willebrand factor by about 12-fold compared to random immobilization. These findings emphasize the importance of controlled protein orientation in biosensor design. They also highlight the power of single site-specific genetic encoding of reactive ncAAs and bioorthogonal chemistry to improve the performance of lectin-based diagnostic tools.

Synthetic Studies on Bioactive Substances: From Research on Water-soluble Compounds to the Field of Lipophilic Ligands

This is a personal review of my chemistry research on retirement from Teikyo University. Under the guidance of Prof. Masaji Ohno of the Faculty of Pharmaceutical Sciences, The University of Tokyo, my research career started with the synthesis of water-soluble basic natural compounds, including the first artificial bleomycin showing potent molecular-oxygen activation effects and DNA binding abilities. While studying abroad at Eidgenössische Technische Hochschule (ETH) under the guidance of Prof. Albert Eschenmoser, I studied the formation of ribose under prebiotic conditions. The condensation reaction between formaldehyde and glycolaldehyde phosphate produced ribose in far greater yield than the formose reaction. In the School of Pharmacy, Showa University, I conducted research in nucleic acid chemistry to synthesize, for example, anomeric spiro-nucleosides using radical chemistry and oligonucleotides that interacted with the κB motif. After moving to Teikyo University in 1999, I engaged in studies on the synthesis of vitamin D derivatives, included in fat-soluble vitamins, with selective biological activities without calcemic side-effects, and discovered, for example, 2α-(3-hydroxypropyl)-19-nor-1α,25-dihydroxyvitamin D3 (MART-10), which exhibits potent anticancer activity in vivo, 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 (AH-1), which shows greater bone-forming effects than natural active vitamin D3 in vivo, and the A-ring-converted vitamin D derivative KK-052, which is an in vivo selective inhibitor of sterol regulatory-element binding protein (SREBP), a master transcription factor of lipogenesis, independent of the vitamin D canonical activity through a vitamin D receptor.

Histidine is effective in promoting muscle growth and protein deposition: In vivo and in vitro experimental models of grass carp (Ctenopharyngodon idella)

For aquatic animals, histidine is an essential amino acid. This study examined its impact on muscle growth and protein deposition in grass carp, both in vivo and in vitro, and explored the underlying mechanisms. A total of 450 grass carp (594.63 ± 0.68 g) were assigned randomly to six groups of three replicates for each group that was fed with six diets containing 1.08 (basal diet), 2.91, 5.87, 8.83, 11.78, and 14.79 g/kg histidine for 63 d. Results indicated that based on PWG and muscle protein content, the histidine demands of adult grass carp were 8.94 (34.12 g/kg protein) and 8.54 g/kg diet (32.60 g/kg protein), respectively. Optimal histidine promoted myofiber hypertrophy, which could be correlated with cell proliferation-associated proteins [PCNA, E2F4 and Cyclin (B, D and E)] and myogenic regulators (MyoD, MyoG, MyHC and Myf6). Optimum histidine enhanced protein deposition, which could be correlated with the facilitation of protein synthesis (IGF-1/PI3K/AKT/TOR) as well as the suppression of ubiquitin-proteasome system and autophagy-lysosome system to inhibit protein degradation. Furthermore, optimal histidine raised muscle bound amino acid content and amino acid chemistry scores, thereby increasing muscle nutritional value.

Bempedoic Acid's Chemistry, Pharmacological Characteristics and Bioanalytical Techniques: An Updated Review

Background: Elevated blood cholesterol has been established as a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Adults with hyperlipidemia have a significantly increased risk of developing cardiovascular diseases (CVD). First-line treatments for hyperlipidemia include statins, which help raise HDL-C levels in cases of severe and familial hypercholesterolemia and decrease LDL-C and TG levels. Numerous adverse effects on muscles have been associated with statins, such as asymptomatic elevations in blood creatine kinase activity and potentially fatal rhabdomyolysis. Non-statin drugs are advised for people whose very high cardiovascular risk or heterozygous familial hypercholesterolemia make statin therapy insufficient. A novel lipid-lowering medication with a distinct mode of action is bempedoic acid. Elevated blood cholesterol is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Individuals with hyperlipidemia are at a higher risk for developing cardiovascular diseases. Statins are the primary treatment for hyperlipidemia, raising HDL-C levels and lowering LDL-C and TG levels. However, statins can adversely affect muscles, including muscle-related complications like increased blood creatine kinase activity and rhabdomyolysis. Therefore, nonstatin drugs may be recommended for individuals. Bempedoic acid is a brand-new, first-in-class, oral small molecule that inhibits cholesterol manufacturing like statins, consequently reducing lowdensity lipoprotein cholesterol (LDL-C) through activating LDL receptors. Methods: This study offers helpful information on how to utilize bempedoic acid to decrease LDLC, as well as recommendations for which individuals could benefit and safety monitoring tips during therapy. A novel family of drugs called bempedoic acid is identified as a prodrug that becomes bempedoyl- CoA in the liver via an enzyme called very longchain consisting of acyl-CoA synthetase 1. Bempedoic acid can control cholesterol metabolism. Low-density lipoprotein cholesterol levels appeared to be dramatically reduced by bempedoic acid, according to clinical investigations. The toleration of bempedoic acid was good. Results: A cardiovascular outcomes trial is now evaluating bempedoic acid to determine its impact on major cardiovascular events in patients with or at high risk for cardiovascular disease and statin intolerance. Conclusion: This review describes the chemistry, mechanism of action, pharmacokinetics, analytical potential, and safety of bempedoic acid. Bempedoic acid is an effective and often well-tolerated drug used to further reduce LDL-C levels in patients taking the maximum dosage of tolerated statins or to control LDL-C levels in persons who can not take statins. The results of the clear Outcomes research, which is looking into whether bempedoic acid might reduce the frequency of serious cardiovascular events, are expected in 2025.

Amphiphilic Oligonucleotide Derivatives-Promising Tools for Therapeutics.

Recent advances in genetics and nucleic acid chemistry have created fundamentally new tools, both for practical applications in therapy and diagnostics and for fundamental genome editing tasks. Nucleic acid-based therapeutic agents offer a distinct advantage of selectively targeting the underlying cause of the disease. Nevertheless, despite the success achieved thus far, there remain unresolved issues regarding the improvement of the pharmacokinetic properties of therapeutic nucleic acids while preserving their biological activity. In order to address these challenges, there is a growing focus on the study of safe and effective delivery methods utilising modified nucleic acid analogues and their lipid bioconjugates. The present review article provides an overview of the current state of the art in the use of chemically modified nucleic acid derivatives for therapeutic applications, with a particular focus on oligonucleotides conjugated to lipid moieties. A systematic analysis has been conducted to investigate the ability of amphiphilic oligonucleotides to self-assemble into micelle-like structures, as well as the influence of non-covalent interactions of such derivatives with serum albumin on their biodistribution and therapeutic effects.

Effect of modifiers on the stability of 1‑butyl‑3-methylimidazolium-based ionic liquids

The distinctive capabilities of 1‑butyl‑3-methylimidazolium (bmim) cation-based ionic liquids (ILs) to dissolve lignocellulosic biomass offer the potential for the development of novel green bioprocessing technologies based on their utilization as green solvents. The limited range of thermal stability of ILs necessitates the use of various co-solvents to maintain solubility. In the present study, an original approach to determine the degree of degradation of alkylimidazolium ILs was proposed, based on the application of gravimetric analysis method to determine the content of volatile degradation products and high-performance liquid chromatography-high-resolution mass spectrometry (HPLCHRMS) to determine the total degree of degradation. The proposed approach, as well as the combination of HPLCHRMS with gas chromatography-mass spectrometry (GC–MS), was employed to comprehensively characterize the impact of additives and impurities (water, dimethyl sulfoxide, hydrochloric and acetic acids, diethylamine) on the degradation of bmim acetate, chloride, and methyl sulfate during thermal treatment under typical biomass dissolution conditions (150 °C, 24 h). The presence of additives or impurities in the composition of ILs has been found to predominantly contribute to a decrease in the number of volatile compounds formed, while increasing the variety and relative content of non-volatile degradation products. The use of protic solvents and acids results in a decrease in the overall degree of degradation of ionic liquids and in the fraction of volatile compounds formed. This allows for the classification of binary mixtures based on these additives as "green" solvents at temperatures below 150 °C.

Post Tungsten CMP Cleaning: Optimization for Cleaning Efficiency and Corrosion Reduction

Tungsten chemical-mechanical planarization (W CMP) is among the first applications of the CMP process implemented in high volume semiconductor manufacturing. Alkaline chemicals such as diluted NH4OH have been the predominant choice of post W CMP clean due to charge repulsion between W and dielectric/abrasive surface in high pH. However, W dissolution occurs spontaneously above pH ∼ 4.0. Consequently, W corrosion can happen during post-CMP cleaning. From that perspective, acidic chemistry (e.g., pH < 4.0) seems a more benign choice to protect W, although at such low pH, isoelectric potential curves suggest coulombic attraction between W and oxide/silica surfaces, making it unfavorable for particle removal. The above pH dilemma for post-CMP cleaning and W protection can be managed by adding corrosion inhibitor to an alkaline chemical. Results from blanket and patterned wafers suggest reduction in surface defects and W dissolution can be accomplished simultaneously by an alkaline clean chemical with corrosion inhibitor (pH ∼ 9.78), which shows high cleaning efficiency and reduced W loss than citric acid-based chemical (pH ∼ 2.66), DIW, and diluted NH4OH. In addition, we show that DIW alone can induce severe W dissolution in features of fine geometry. Possible counter measures against such DIW-induced W corrosion are discussed.

SYNTHESIS AND CHARACTERIZATION OF POLYEPICHLOROHYDRIN DIOLS

Polyepichlorohydrin (PECH) is a functional polymer with high value in energy materials. Cationic ring-opening polymerization of epichlorohydrin (ECH) with a diol initiator and Lewis or protic acids catalyst, proceeds through an activated monomer mechanism (AM) allowing control of the polymer's average molecular weight and polydispersity index. In the present investigation, PECH diol was synthesized under the catalysis of boron trifluoride etherate, with the ECH monomer:ethylene glycol as an initiator molar ratio of 1:0.045, achieving a low molecular weight nM = 1935 g/mol, low polydispersity index PDI = 1.25, predominantly in the linear chain configuration with the terminal hydroxyl group.

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis.

The Mangshan pit viper, Protobothrops mangshanensis, is a rare, highly endangered snake native to the mountainous regions of Hunan Province in China. Snakes possess abdominal scent glands, which have been chemically studied in several species. These glands can contain various lipids and peptides, but very often also complex mixtures of carboxylic acids. We report here the occurrence of novel methyl-branched unsaturated acids found in the secretions of six captive individuals living in a zoo. The structures of these compounds, 4.6-dimethylalk-5-enoates in a homologous series from C11-C16, were characterized by GC-MS and GC-IR analysis and various microderivatization reactions including hydrogenation and esterification leading to methyl and pyridylmethyl esters. In addition, dimethyloxazoline formation helped to localize the double bond. The synthesis of methyl 4,6-dimethyldodec-5-enoate allowed the correct assignment of structures and showed the (E)-configuration of the double bond for the major naturally occurring diastereomers. These acids occur in small amounts compared to the major glandular components, cholesterol, and 1-O-hexadecylglycerol, as well as other common long-chain alcohols and amides. Although a general defensive function has been proposed for snake abdominal scent glands, the specific chemistry and moderate amounts of acids reported here may suggest a function in chemical signaling for the Mangshan pit viper. In addition, proline-containing diketopiperazines were identified for the first time in snake scent glands, although an artificial formation from amino acids likely present in the secretion cannot be excluded.

Modulating Electrostatic Properties and Noncovalent Interactions via Structural Isomerism: The Microwave Spectra and Molecular Structures of (E)- and (Z)-1,2,3,3,3-Pentafluoropropene and Their Gas-Phase Heterodimers with the Argon Atom.

Microwave spectra of both the E and Z isomers of 1,2,3,3,3-pentafluoropropene along with all three of the singly substituted 13C isotopologues for each are obtained using broadband chirped-pulse Fourier transform microwave spectroscopy from 2.0-18.1 GHz. Associated quantum chemistry calculations show that the barrier to internal rotation of the CF3 group is significantly higher for the Z isomer, which is stabilized by an intramolecular hydrogen bond, although the barriers in both isomers are sufficiently high to prevent the observation of any effects due to internal rotation. The normal isotopologues of the argon heterodimers for both isomers are also observed in the broadband spectrum and a Balle-Flygare cavity Fourier transform microwave spectrometer is used to obtain the 5.0-20.6 GHz spectra of the corresponding 13C isotopologues. In each case, the argon atom locates so as to maximize its interactions with areas of significant electron density. However, mapped electrostatic potential surfaces indicate that the areas of greatest nucleophilicity are different for the two isomers, suggesting that they may interact differently in forming heterodimers with protic acids.

Responses of soil microbial metabolism, function and soil quality to long-term addition of organic materials with different carbon sources

Biochar and green manure have been widely applied in agricultural production and are important means to achieve sustainable agriculture. However, there is limited research systematically and comprehensively exploring the response of soil microbiota and the changes in soil metabolomics after the addition of two different carbon source amendments to the soil, and the differential mechanisms of soil metabolomics between them remain unclear. In this study, a long-term field experiment (initiated in 2019) was conducted to investigate the effects of biochar and green manure application on soil nutrients and soil functions driven by soil microbes. Compared to the pure fertilizer treatment, biochar increased soil total carbon by 14.54% to 27.04% and soil available potassium by 4.67% to 27.46%. Ryegrass significantly increased soil available phosphorus and organic matter. Under different fertilization regimes, the ecological niches of soil microbes changed significantly. Network analysis revealed that long-term ryegrass returning reduced the complexity of soil microbial networks. Ryegrass and biochar increased dispersal limitation in fungal assemblages (reaching 93.33% and 86.67%, respectively), with biochar particularly enhancing variable selection in bacterial assemblages (accounting for 53.33%). Variation partitioning analysis based on redundancy analysis indicated that humic substances had the highest explanatory power for microbial community variation, with humic substances explaining 38.49% of bacteria and 52.19% of fungi variation. The ryegrass treatment mainly changed the abundance of carbohydrates (CH), amines (AM), c (AH), and lipids (LP), while the BC treatment mainly altered the abundance of organic acids (AC), amines (AM), and carbohydrates (CH). Meanwhile, both treatments significantly reduced the bisphenol A, one of the soil pollutants. Ryegrass incorporation significantly increased the abundance of genes related to soil C, N, P, and S cycling, especially genes involved in carbon decomposition, while biochar significantly enhanced the abundance of nitrogen fixation genes nifH and Hao in soil. Random forest model results indicated that carbohydrates, alcohols, aromatics (AR), and ester (ES) were the main categories of metabolites in soil influenced by differential microbes, and Finegoldia served as a common important metabolic driving species. In summary, this study reveals the processes of soil function, microbial community succession, and metabolism driven by ryegrass and biochar, providing important insights for optimizing soil management and improving soil quality.Graphical

Solvatochromic and biological studies of new meso-benzodioxole-BODIPY-2-Schiff dye

This paper focuses on solvatochromic studies of a new synthesised BODIPY dye with piperonal and ortho-hydroxy aryl Schiff base substituents (BD-2-Schiff). The studied dye has been analysed by spectroscopic and computational techniques to have a deep insight into the impact of the solvents’ polarity and the specific interactions on the dye characteristics. The synthesized dye turns to be sensitive to external specific interactions, caused by protic solvents and acid, which change spectral characteristics of BODIPY-2-Schiff. The calculations by the density functional theory (DFT) and the time-dependent density functional theory (TD-DFT) have been accomplished for the interpretation of the obtained experimental results. The synthesized dye has been evaluated as a photosensitizer for the light induced inactivation of Staphylococcus aureus (S. aureus) and Acinetobacter baumannii (A. baumannii). The synthesized BODIPY dye has shown a significant photocidal activity (above 90 %) against these pathogenic bacteria at low microgram concentrations and excitation with low doses of visible light (0.72 J/cm2; λ = 519 nm).

Molecular studies of Allographa effusosoredica sp. nov. (Graphidaceae) along with its Trentepohlia photobiont and a comprehensive checklist for Indian Allographa

The current study describes a new species, Allographa effusosoredica, from the Western Ghats, India, along with its Trentepohlia photobiont. This study is based on morphological, chemical and molecular analyses using mtSSU, LSU and RPB2 sequence data for Allographa effusosoredica mycobiont and ITS sequence data for Trentepohlia photobiont. Allographa effusosoredica is characterized by a thin effuse thallus with diffuse soredia, 8-spored asci, transversely 7–11 septate ascospores, and norstictic acid chemistry. It is surprisingly similar to the widespread Graphis glaucescens, which differs in the absence of soredia and norstictic acid, but clusters phylogenetically within Allographa, allied to Allographa xanthospora, making the limits between Allographa and the distantly related genus Graphis more diffuse and raising doubts about the correct placement of G. glaucescens. The photobiont of the novel species is allied to Trentepohlia cf. arborum HZ-2017 isolate YN1047. This is the first species of Allographa sequenced from India.

Versatile synthesis of 2-functionalized dihydrothiazolo[2,3-b]quinazolines through regioselective electrophilic intramolecular heterocyclization of 3-alkenyl-2-thioxoquinazolin-4-ones

Electrophilic intramolecular heterocyclizations of 3-alkenyl-2-thioxoquinazolin-4-ones, induced by halogens, NBS, sulfuryl chloride, protic acids, selenium, or tellurium halides, proceed with high regioselectivity. This process leads to the formation of 2-functionalized dihydrothiazolo[2,3-b]quinazolines, showcasing the versatility and reliability of this synthetic route across various electrophilic reagents.

Investigation of transverse exchange-springs in electrodeposited nano-heterostructured films through first-order reversal curve analysis

The prerequisite of efficient exchange-spring nano-heterostructures, i.e., tuning both hard and soft phases at a nanometer level, has posed significant preparation challenges to ensure effective exchange-coupling. Here, we present a novel approach to fabricate transverse exchange-spring nano-heterostructures using single starting material through an “in situ” electrodeposition technique at room temperature. Utilizing modified acidic bath chemistry and controlled hydrogen evolution, we successfully prepared stress-free, shiny, fine-grained amorphous, and nanocrystalline Co-rich cobalt phosphorus films. These nano-heterostructured films exhibit a unique non-collinear anisotropy-driven transverse exchange-spring behavior, investigated systematically under ambient conditions. The comprehensive functional analyses reveal that intricate interplay between in-plane (IP) anisotropy of amorphous phase and out-of-plane (OOP) anisotropy generating from a nanocrystalline structure compete with each other, while producing characteristic stripe domain structures to novel corrugated stripe domain shapes. The angle-dependent first-order reversal curve distributions demonstrate new insights into the magnetic reversal mechanisms, further confirming the non-exchange-spring and exchange-spring nature of the films depending on the prevalent interfacial exchange coupling. Formation of anisotropy-driven metastable-state due to competition between IP and OOP anisotropy at a particular OOP orientation has led the normal exchange-spring structures to a transverse exchange-spring structure. Micromagnetic simulations, in excellent agreement with experimental data, further elucidate the formation of characteristic stripe domain patterns and the influence of anisotropy on the magnetic properties. The innovative methodology and detailed functional analysis presented here offer significant understanding to the field of exchange-spring magnetic materials, including anisotropy-driven metastable states, demonstrating the potential for scalable and cost-effective fabrication of advanced nano-heterostructures with tailored magnetic properties.

Development of a Shigella conjugate vaccine targeting Shigella flexneri 6 that is immunogenic and provides protection against virulent challenge

Immunity protective against shigella infection targets the bacterial O-specific polysaccharide (OSP) component of lipopolysaccharide. A multivalent shigella vaccine would ideally target the most common global Shigella species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. We previously reported development of shigella conjugate vaccines (SCVs) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using a platform squaric acid chemistry conjugation approach and carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. Here we report development of a SCV targeting S. flexneri 6 (SCV-Sf6) using the same platform approach. We demonstrated that SCV-Sf6 was recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG and IgM responses, as well as rTTHc-specific IgG responses. Immune responses were increased when administered with aluminum phosphate adjuvant. Vaccination induced bactericidal antibody responses against S. flexneri 6, and vaccinated animals were protected against lethal challenge with virulent S. flexneri 6. Our results assist in the development of a multivalent vaccine protective against shigellosis.

Optimising CNT-FET biosensor design through modelling of biomolecular electrostatic gating and its application to β-lactamase detection

Carbon nanotube field effect transistors (CNT-FET) hold great promise as next generation miniaturised biosensors. One bottleneck is modelling how proteins, with their distinctive electrostatic surfaces, interact with the CNT-FET to modulate conductance. Using advanced sampling molecular dynamics combined with non-canonical amino acid chemistry, we model protein electrostatic potential imparted on single walled CNTs (SWCNTs). We focus on using β-lactamase binding protein (BLIP2) as the receptor as it binds the antibiotic degrading enzymes, β-lactamases (BLs). BLIP2 is attached via the single selected residue to SWCNTs using genetically encoded phenyl azide photochemistry. Our devices detect two different BLs, TEM-1 and KPC-2, with each BL generating distinct conductance profiles due to their differing surface electrostatic profiles. Changes in conductance match the model electrostatic profile sampled by the SWCNTs on BL binding. Thus, our modelling approach combined with residue-specific receptor attachment could provide a general approach for systematic CNT-FET biosensor construction.

Prevention of ischemic stroke in patients with myeloproliferative neoplasms

Introduction. Myeloproliferative neoplasms (MPNs) are a rare but significant cause of strokes.Aim. To describe risk factors for stroke development, as well as prevention strategies based on available literature data on patients with MPN.Main findings. Online databases (PubMed, E-Library) were searched for studies on cerebral thrombotic complications in the setting of myeloproliferative disorders. Induction of specific cytoreductive treatment with low doses of acetylsalicylic ac id should be considered as a mandatory component of secondary prevention of noncardioembolic stroke.