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Biochemical Society Transactions Jul 2024The major energy-producing reactions of biochemistry occur at biological membranes. Computational protein design now provides the opportunity to elucidate the underlying...
The major energy-producing reactions of biochemistry occur at biological membranes. Computational protein design now provides the opportunity to elucidate the underlying principles of these processes and to construct bioenergetic pathways on our own terms. Here, we review recent achievements in this endeavour of 'synthetic bioenergetics', with a particular focus on new enabling tools that facilitate the computational design of biocompatible de novo integral membrane proteins. We use recent examples to showcase some of the key computational approaches in current use and highlight that the overall philosophy of 'surface-swapping' - the replacement of solvent-facing residues with amino acids bearing lipid-soluble hydrophobic sidechains - is a promising avenue in membrane protein design. We conclude by highlighting outstanding design challenges and the emerging role of AI in sequence design and structure ideation.
PubMed: 38958574
DOI: 10.1042/BST20231347 -
Atomic-scale origin of the enantiospecific decomposition of tartaric acid on chiral copper surfaces.Chemical Communications (Cambridge,... Jul 2024The origin of the enantiospecific decomposition of L- and D-tartaric acid on chiral Cu surfaces is elucidated on a structure-spread domed Cu(110) crystal by spatially...
The origin of the enantiospecific decomposition of L- and D-tartaric acid on chiral Cu surfaces is elucidated on a structure-spread domed Cu(110) crystal by spatially resolved XPS and atomic-scale STM imaging. Extensive enantiospecific surface restructuring leads to the formation of surfaces vicinal to Cu(14,17,2) which are responsible for the enantiospecificity.
PubMed: 38958572
DOI: 10.1039/d4cc02384f -
Advanced Science (Weinheim,... Jul 2024Detection of circulating tumor DNA (ctDNA) mutations, which are molecular biomarkers present in bodily fluids of cancer patients, can be applied for tumor diagnosis and...
Detection of circulating tumor DNA (ctDNA) mutations, which are molecular biomarkers present in bodily fluids of cancer patients, can be applied for tumor diagnosis and prognosis monitoring. However, current profiling of ctDNA mutations relies primarily on polymerase chain reaction (PCR) and DNA sequencing and these techniques require preanalytical processing of blood samples, which are time-consuming, expensive, and tedious procedures that increase the risk of sample contamination. To overcome these limitations, here the engineering of a DNA/γPNA (gamma peptide nucleic acid) hybrid nanoreporter is disclosed for ctDNA biosensing via in situ profiling and recording of tumor-specific DNA mutations. The low tolerance of γPNA to single mismatch in base pairing with DNA allows highly selective recognition and recording of ctDNA mutations in peripheral blood. Owing to their remarkable biostability, the detached γPNA strands triggered by mutant ctDNA will be enriched in kidneys and cleared into urine for urinalysis. It is demonstrated that the nanoreporter has high specificity for ctDNA mutation in peripheral blood, and urinalysis of cleared γPNA can provide valuable information for tumor progression and prognosis evaluation. This work demonstrates the potential of the nanoreporter for urinary monitoring of tumor and patient prognosis through in situ biosensing of ctDNA mutations.
PubMed: 38958527
DOI: 10.1002/advs.202310225 -
Langmuir : the ACS Journal of Surfaces... Jul 2024Amino acids make up a promising family of molecules capable of direct air capture (DAC) of CO from the atmosphere. Under alkaline conditions, CO reacts with the anionic...
Amino acids make up a promising family of molecules capable of direct air capture (DAC) of CO from the atmosphere. Under alkaline conditions, CO reacts with the anionic form of an amino acid to produce carbamates and deactivated zwitterionic amino acids. The presence of the various species of amino acids and reactive intermediates can have a significant effect on DAC chemistry, the role of which is poorly understood. In this study, all-atom molecular dynamics (MD) based computational simulations and vibrational sum frequency generation (vSFG) spectroscopy studies were conducted to understand the role of competitive interactions at the air-aqueous interface in the context of DAC. We find that the presence of potassium bicarbonate ions, in combination with the anionic and zwitterionic forms of amino acids, induces concentration and charge gradients at the interface, generating a layered molecular arrangement that changes under pre- and post-DAC conditions. In parallel, an enhancement in the surface activity of both anionic and zwitterionic forms of amino acids is observed, which is attributed to enhanced interfacial stability and favorable intermolecular interactions between the adsorbed amino acids in their anionic and zwitterionic forms. The collective influence of these competitive interactions, along with the resulting interfacial heterogeneity, may in turn affect subsequent capture reactions and associated rates. These effects underscore the need to consider dynamic changes in interfacial chemical makeup to enhance DAC efficiency and to develop successful negative emission and storage technologies.
PubMed: 38958522
DOI: 10.1021/acs.langmuir.4c00907 -
Journal of the Science of Food and... Jul 2024The Cosmos sulphureus Cav. plant is studied for its high polyphenolic content with antioxidant properties. Its flowers, rich in phenolic acids, flavonoids, and tannins,...
BACKGROUND
The Cosmos sulphureus Cav. plant is studied for its high polyphenolic content with antioxidant properties. Its flowers, rich in phenolic acids, flavonoids, and tannins, hold promise as antioxidants in food preservation. The inclusion of these compounds in chickpea-based coatings with a previously studied preservative effect would be an excellent option as a food preservation method and microencapsulation addresses challenges like dispersion and degradation of polyphenols in the coating. The objective of this research was to evaluate the in vitro antioxidant activity of Cosmos sulphureus leaves, seed, and flower extracts and explore the protective effects of chickpea-based coatings containing microcapsules of flower polyphenolic extract on the chemical quality of stored roasted sunflower seeds during storage.
RESULTS
The ethanolic leaf extract exhibited the highest antiradical activity, followed by the aqueous flower extract. After a storage period of 15 days, at 40 °C, the chickpea-based coatings effectively delayed lipid oxidation in the roasted sunflowers seeds, and the inclusion of polyphenolic microcapsules with 0.01% extract (SMC 0.01%) in the coating significantly improved the protective effect. By day 15 of storage, SMC 0.01% showed comparable peroxide value, conjugated dienes, and linoleic acid content to samples containing the synthetic antioxidant BHT (butylated hydroxytoluene). Samples that only contained chickpea-based coating and coating with polyphenolic microcapsules with 0.005% extract exhibited significantly greater reduction in fatty acid content compared to the 0.01% SMC treatment.
CONCLUSION
The chickpea-based coating with polyphenolic microcapsules demonstrated antioxidant activity akin to synthetic BHT, offering a promising biopackaging solution for lipid-rich foods like roasted sunflower seeds. © 2024 Society of Chemical Industry.
PubMed: 38958470
DOI: 10.1002/jsfa.13715 -
Birth Defects Research Jul 2024Autism spectrum disorder (ASD) is the fastest-growing child neuropsychiatric condition. Cognitive dysfunctions such as memory impairments are experienced by patients...
BACKGROUND
Autism spectrum disorder (ASD) is the fastest-growing child neuropsychiatric condition. Cognitive dysfunctions such as memory impairments are experienced by patients along with social disturbances and repetitive/stereotypic movements. We have used the radial arm maze (RAM), for measurement of working and reference memory errors in an animal model of autism. In addition, the potential effects of agmatine, an endogenous NMDA antagonist, on RAM performance and autistic-like behaviors were assessed.
METHODS
Autism was modeled by valproic acid (VPA) administration at gestational Day 12.5. Autism-associated behaviors in male offspring were examined in an open field test (OFT) and three-chambered test (TCT) on postnatal days 50-51. Thereafter, the animals were trained in the RAM (PND 55) until they attained the criteria of 80% correct choices during five consecutive trials. Forty-eight hours after the acquisition of criteria, agmatine was injected 30 min before subsequent behavioral testing, which included the retention phase of the RAM, OFT, and TCT.
RESULTS
VPA-treated and intact rats showed the same performance in RAM, and acute injection of agmatine rescued social and anxiety-like behavior induced by VPA without the effect on RAM.
CONCLUSION
In a rat model of autism, spatial learning, and memory did not change. Agmatine rescued social and anxiety-like behavior in autistic animals.
Topics: Animals; Agmatine; Male; Disease Models, Animal; Rats; Maze Learning; Autistic Disorder; Behavior, Animal; Memory; Valproic Acid; Female; Pregnancy
PubMed: 38958465
DOI: 10.1002/bdr2.2379 -
Microbiology Spectrum Jul 2024Growing numbers of infections caused by antibiotic-resistant strains are a major concern for healthcare systems that will require new antibiotics for treatment as well...
Growing numbers of infections caused by antibiotic-resistant strains are a major concern for healthcare systems that will require new antibiotics for treatment as well as preventative measures that reduce the number of infections. Lipopeptides are antimicrobial molecules, of which some are used as antibiotics, including the last resort antibiotics daptomycin and polymyxins. Here we have studied the antimicrobial effect of the cyclic lipopeptide viscosin on growth and morphology. Most lipopeptides function as surfactants that create pores in membrane layers, which is regarded as their main antimicrobial activity. We show that viscosin can inhibit growth of without disintegration of the cytoplasmic membrane. Instead, the cells developed abnormal shapes and misplaced new division sites. The cell wall of these bacteria appeared less dense in electron microscopy images, suggesting that viscosin interfered with normal cell wall synthesis. Corroborating this observation, a luciferase reporter assay was used to show that the two-component systems LiaFSR and CiaRH, which are known to be activated upon cell wall stress, were strongly induced by viscosin. Furthermore, a mutant displaying 1.8-fold decreased susceptibility to viscosin was generated by sequential exposure to increasing concentrations of the lipopeptide. The mutant suffered from significant fitness loss and had mutations in genes involved in fatty acid synthesis, teichoic acid synthesis, and cell wall synthesis as well as transcription and translation. How these mutations might be linked to decreased viscosin susceptibility is discussed.IMPORTANCE is a leading cause of bacterial pneumonia, sepsis, and meningitis in children, and the incidence of infections caused by antibiotic-resistant strains is increasing. Development of new antibiotics is therefore necessary to treat these types of infections in the future. Here, we have studied the activity of the antimicrobial lipopeptide viscosin on and show that in addition to having the typical membrane destabilizing activity of lipopeptides, viscosin inhibits pneumococcal growth by obstructing normal cell wall synthesis. This suggests a more specific mode of action than just the surfactant activity. Furthermore, we show that does not easily acquire resistance to viscosin, which makes it a promising molecule to explore further, for example, by synthesizing less toxic derivates that can be tested for therapeutic potential.
PubMed: 38958463
DOI: 10.1128/spectrum.00624-24 -
MSphere Jul 2024McKenzie Lehman works in the field of bacterial pathogenesis and metabolism. In this mSphere of Influence article, she reflects on how three papers entitled "Glycolytic...
McKenzie Lehman works in the field of bacterial pathogenesis and metabolism. In this mSphere of Influence article, she reflects on how three papers entitled "Glycolytic dependency of high-level nitric oxide resistance and virulence in by N. P. Vitko, N. A. Spahich, and A. R. Richardson (mBio 6:e00045-15, 2015, https://doi.org/10.1128/mbio.00045-15), "The cystine transporters TcyABC and TcyP facilitate nutrient sulfur acquisition during infection" by J. M. Lensmire, J. P. Dodson, B. Y. Hsueh, M. R. Wischer, et al. (Infect Immun 88:e00690-19, 2020, https://doi.org/10.1128/iai.00690-19), and "The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in " by C. F. Schuster, L. E. Bellows, T. Tosi, I. Campeotto, et al. (Sci Signal 16:ra81, 2016, https://doi.org/10.1126/scisignal.aaf7279) impacted her work on bacterial metabolism and pathogenesis.
PubMed: 38958458
DOI: 10.1128/msphere.00239-24 -
Microbiology and Molecular Biology... Jul 2024SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the... (Review)
Review
SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.
PubMed: 38958456
DOI: 10.1128/mmbr.00205-22 -
Journal of Cosmetic Dermatology Jul 2024Given the significant increase in the quantity of cosmetic procedures utilizing hyaluronic acid fillers, including in the nasal region, the initial evaluation of...
BACKGROUND
Given the significant increase in the quantity of cosmetic procedures utilizing hyaluronic acid fillers, including in the nasal region, the initial evaluation of patients using high frequency ultrasound becomes a crucial instrument in evaluating and handling nonsurgical rhinoplasty.
AIMS
The aim of this article is to introduce an assessment methodology for nasal filling guided by high frequency ultrasound.
PATIENTS/METHODS
A prospective and single-center study was conducted with 12 Latin American patients. The patients underwent nasal filling with hyaluronic acid following high power ultrasound mapping.
RESULTS AND CONCLUSIONS
In the evaluation of the GAIS scale, all patients reported improvement with the treatment. No infections, nodules, ischemia, or other relevant adverse effects were noted. Real-time ultrasound-guided filler techniques have been developed to reduce the risk of vascular compromise, confirming the distribution pattern of blood vessels. It's also crucial to visualize the cannula at the same moment as the vessels, even if the previous vascular mapping was performed. Therefore, the utilization of high frequency ultrasound can act as a pivotal tool in augmenting procedure safety.
PubMed: 38958454
DOI: 10.1111/jocd.16430