Instantaneous Inactivation Research Articles

Instantaneous Inactivation of Herpes Simplex Virus by Silicon Nitride Bioceramics.

Hydrolytic reactions taking place at the surface of a silicon nitride (Si3N4) bioceramic were found to induce instantaneous inactivation of Human herpesvirus 1 (HHV-1, also known as Herpes simplex virus 1 or HSV-1). Si3N4 is a non-oxide ceramic compound with strong antibacterial and antiviral properties that has been proven safe for human cells. HSV-1 is a double-stranded DNA virus that infects a variety of host tissues through a lytic and latent cycle. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of HSV-1 DNA after instantaneous contact with Si3N4 showed that ammonia and its nitrogen radical byproducts, produced upon Si3N4 hydrolysis, directly reacted with viral proteins and fragmented the virus DNA, irreversibly damaging its structure. A comparison carried out upon testing HSV-1 against ZrO2 particles under identical experimental conditions showed a significantly weaker (but not null) antiviral effect, which was attributed to oxygen radical influence. The results of this study extend the effectiveness of Si3N4's antiviral properties beyond their previously proven efficacy against a large variety of single-stranded enveloped and non-enveloped RNA viruses. Possible applications include the development of antiviral creams or gels and oral rinses to exploit an extremely efficient, localized, and instantaneous viral reduction by means of a safe and more effective alternative to conventional antiviral creams. Upon incorporating a minor fraction of micrometric Si3N4 particles into polymeric matrices, antiherpetic devices could be fabricated, which would effectively impede viral reactivation and enable high local effectiveness for extended periods of time.

Raman Fingerprints of the SARS-CoV-2 Delta Variant and Mechanisms of Its Instantaneous Inactivation by Silicon Nitride Bioceramics.

Raman spectroscopy uncovered molecular scale markers of the viral structure of the SARS-CoV-2 Delta variant and related viral inactivation mechanisms at the biological interface with silicon nitride (Si3N4) bioceramics. A comparison of Raman spectra collected on the TY11-927 variant (lineage B.1.617.2; simply referred to as the Delta variant henceforth) with those of the JPN/TY/WK-521 variant (lineage B.1.617.1; referred to as the Kappa variant or simply as the Japanese isolate henceforth) revealed the occurrence of key mutations of the spike receptor together with profound structural differences in the molecular structure/symmetry of sulfur-containing amino acid and altered hydrophobic interactions of the tyrosine residue. Additionally, different vibrational fractions of RNA purines and pyrimidines and dissimilar protein secondary structures were also recorded. Despite mutations, hydrolytic reactions at the surface of silicon nitride (Si3N4) bioceramics induced instantaneous inactivation of the Delta variant at the same rate as that of the Kappa variant. Contact between virions and micrometric Si3N4 particles yielded post-translational deimination of arginine spike residues, methionine sulfoxidation, tyrosine nitration, and oxidation of RNA purines to form formamidopyrimidines. Si3N4 bioceramics proved to be a safe and effective inorganic compound for instantaneous environmental sanitation.

Mechanisms of instantaneous inactivation of SARS-CoV-2 by silicon nitride bioceramic.

The hydrolytic processes occurring at the surface of silicon nitride (Si3N4) bioceramic have been indicated as a powerful pathway to instantaneous inactivation of SARS-CoV-2 virus. However, the virus inactivation mechanisms promoted by Si3N4 remain yet to be elucidated. In this study, we provide evidence of the instantaneous damage incurred on the SARS-CoV-2 virus upon contact with Si3N4. We also emphasize the safety characteristics of Si3N4 for mammalian cells. Contact between the virions and micrometric Si3N4 particles immediately targeted a variety of viral molecules by inducing post-translational oxidative modifications of S-containing amino acids, nitration of the tyrosine residue in the spike receptor binding domain, and oxidation of RNA purines to form formamidopyrimidine. This structural damage in turn led to a reshuffling of the protein secondary structure. These clear fingerprints of viral structure modifications were linked to inhibition of viral functionality and infectivity. This study validates the notion that Si3N4 bioceramic is a safe and effective antiviral compound; and a primary antiviral candidate to replace the toxic and allergenic compounds presently used in contact with the human body and in long-term environmental sanitation.

Bactericidal effect of glycerol monolaurate complex disinfectants on Salmonella of chicken

Glycerol monolaurate (GML) is a monoglycerol ester of the fatty lauric acids, which has a wide-spectrum antimicrobial capacity, but fails to inactivate Gram-negative bacteria, especial Salmonella. To enhance the population reduction rate of GML for Salmonella, this reagent was combined with three disinfectants: lactic acid (LA), cetylpyridinium chloride (CPC), and trisodium phosphate (TSP), which can present acid, neutral, and alkaline in solution, respectively. The results showed that the 1% GML and a complex disinfectant (0.5% GML-0.025% LA) could powerfully inactivate Salmonella. Their population reduction rates respectively were able to achieve 99.92% and 98.29% with the vortex treatment, indicating that the vortex treatment could improve GML to destruct the outer membrane of Salmonella. During the simulation test of the soaking and rinse processing of chicken, for a short time (0 h), the effect of 0.5% GML-0.025% LA compound was better and more suitable for instantaneous inactivation than others, while for a long time (4 h), 1% GML exhibited a better bactericidal effect, which indicated it to be more suitable for long-term bacteriostasis. The characterization of color and texture for chicken samples were determined using Colormeter Ci7600, TA.XT Plus and Hyper-spectral Imager, which demonstrated that all samples treated by these complex disinfectants were not significantly different from untreated group. In conclusion, GML is a potential and superior disinfectant for the chicken process.

Transient photothermal inactivation of Escherichia coli stained with visible dyes by using a nanosecond pulsed laser

Efficient inactivation of Escherichia coli (E. coli) under visible (532 nm) pulsed light irradiation was achieved by fusion of a visible light-absorbing dye with E. coli. Inactivation experiments showed that 3-log inactivation of E. coli was obtained within 20 min under a 50 kJ/cm2 dose. This treatment time and dose magnitude were 10 times faster and 100 times lower, respectively, than the values previously obtained by using a visible femtosecond laser. The mechanism of bacterial death was modeled based on a transient photothermal evaporation effect, where a quantitative evaluation of the temperature increase was given based on the heat transfer equation. As a result of this theoretical analysis, the maximum temperature of the bacteria was correlated with the absorption ratio, pulse energy, and surface-to-volume ratio. An increase in the surface-to-volume ratio with the decreasing size of organic structures leads to the possibility of efficient inactivation of viruses and bacteria under low-dose and non-harmful-visible pulsed light irradiation. Hence, this method can be applied in many fields, such as the instantaneous inactivation of pathogenic viruses and bacteria in a safe and simple manner without damaging large organic structures.

Instantaneous inactivation of cofilin reveals its function of F-actin disassembly in lamellipodia

Cofilin is a key regulator of the actin cytoskeleton. It can sever actin filaments, accelerate filament disassembly, act as a nucleation factor, recruit or antagonize other actin regulators, and control the pool of polymerization-competent actin monomers. In cells these actions have complex functional outputs. The timing and localization of cofilin activity are carefully regulated, and thus global, long-term perturbations may not be sufficient to probe its precise function. To better understand cofilin's spatiotemporal action in cells, we implemented chromophore-assisted laser inactivation (CALI) to instantly and specifically inactivate it. In addition to globally inhibiting actin turnover, CALI of cofilin generated several profound effects on the lamellipodia, including an increase of F-actin, a rearward expansion of the actin network, and a reduction in retrograde flow speed. These results support the hypothesis that the principal role of cofilin in lamellipodia at steady state is to break down F-actin, control filament turnover, and regulate the rate of retrograde flow.

Methylfolate as Adjunctive Treatment in Major Depression

Back to table of contents Previous article Next article Communications and UpdatesFull AccessMethylfolate as Adjunctive Treatment in Major DepressionEdward H. Reynolds, M.D., F.R.C.Psych.Edward H. ReynoldsSearch for more papers by this author, M.D., F.R.C.Psych.Published Online:1 May 2013https://doi.org/10.1176/appi.ajp.2013.13010084AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: As the principal investigator of the only previous placebo-controlled trial of methylfolate as an adjunctive treatment in major depression 22 years ago (1), I appreciated the new trial by Papakostas et al. (2) in the December 2012 issue confirming the efficacy of the vitamin in some resistant depression.Important differences between the two trials raise interesting questions. Our study was for depressed patients with borderline or definite folate deficiency (red blood cell folate levels <200 pg/mL), but Papakostas et al. did not mention the folate status of their patients. I presume that many would not have been folate deficient. We also used 15 mg of methylfolate, but our trial was for 6 months and demonstrated increasing efficacy at 3 and 6 months in contrast to the 60-day study by Papakostas et al.I first reported in 1967 the beneficial effect of the vitamin on mood and some aspects of cognitive and social function in an open trial of folic acid, 5 mg/day for 1 to 3 years, in folate-deficient patients with epilepsy (3). At the Medical Research Council Neuropsychiatry Research Unit, we then showed not only that folate deficiency was common in depression, as had been reported by Carney (4), but that the deficiency was associated with a poor response to antidepressant therapy (5). I subsequently collaborated with Carney and colleagues in demonstrating that depression was the most common reversible neuropsychiatric manifestation of folate-deficient megaloblastic anemia; in confirming that S-adenosylmethionine had antidepressant properties, thus implying that methylation is a key to understanding mood (6); and in identifying a subgroup of patients with depression, high plasma homocysteine levels, folate deficiency, and impaired neurotransmitter metabolism. This culminated in our positive trial of methylfolate, the transport form of folate into the nervous system, as adjunctive therapy in depression (1).A crucial question for the future is to what extent the antidepressant properties of methylfolate depend on the folate status of the patient. Our own pilot observations suggest that methylfolate may have antidepressant properties as monotherapy, irrespective of folate status, but that responders show a greater rise in red cell folate levels than nonresponders (7). An important clue is the mood-elevating properties of nitrous oxide. This euphoriant effect is probably related to the instantaneous inactivation of methionine synthase, leading to an acute rise in methylfolate in the brain (7). Finally, methylation in the nervous system is a key not just to the biology of mood but to other aspects of cognitive function, including dementia. After 45 years, it is time for academic departments of psychiatry to invest more in this nonpharmaceutical approach to mental illness.From the Department of Clinical Neurosciences, King’s College, University of London.The author reports no financial relationships with commercial interests.References1 Godfrey PSA, Toone BK, Carney MWP, Flynn TG, Bottiglieri T, Laundy M, Chanarin I, Reynolds EH: Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990; 336:392–395Crossref, Medline, Google Scholar2 Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A, Baer L, Dalton ED, Sacco GR, Schoenfeld D, Pencina M, Meisner A, Bottiglieri T, Nelson E, Mischoulon D, Alpert JE, Barbee JG, Zisook S, Fava M: l-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry 2012; 169:1267–1274Link, Google Scholar3 Reynolds EH: Effects of folic acid on the mental state and fit-frequency of drug-treated epileptic patients. Lancet 1967; 1:1086–1088Crossref, Medline, Google Scholar4 Carney MWP: Serum folate values in 423 psychiatric patients. Br Med J 1967; 4:512–516Crossref, Medline, Google Scholar5 Reynolds EH, Preece JM, Bailey J, Coppen A: Folate deficiency in depressive illness. Br J Psychiatry 1970; 117:287–292Crossref, Medline, Google Scholar6 Reynolds EH, Carney MWP, Toone BK: Methylation and mood. Lancet 1984; 2:196–198Crossref, Medline, Google Scholar7 Reynolds EH: Vitamin B12, folic acid, and the nervous system. Lancet Neurol 2006; 5:949–960Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByFolic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles24 January 2022 | Biomolecules, Vol. 12, No. 2Behavioral and neurochemical effects of folic acid in a mouse model of depression induced by TNF-αBehavioural Brain Research, Vol. 414Depressão e distúrbios do sonoFolic acid ameliorates depression-like behaviour in a rat model of chronic unpredictable mild stress15 January 2020 | BMC Neuroscience, Vol. 21, No. 1Perspectives in Psychiatric Care, Vol. 54, No. 2Problemy reproduktsii, Vol. 24, No. 3Fundamental & Clinical Pharmacology, Vol. 29, No. 6 Volume 170Issue 5 May 2013Pages 560-560 Metrics PDF download History Accepted 1 February 2013 Published online 1 May 2013 Published in print 1 May 2013

Instantaneous inactivation of cofilin reveals its function of F-actin disassembly in lamellipodia

Instantaneous inactivation of cofilin reveals its function of F-actin disassembly in lamellipodia

Slowing of Instantaneous Inactivation Causes Macroscopic Current Decay in Kv7.1 Alanine Mutants

Alanine scanning mutagenesis in Kv7.1 S4-S5 linker and the pore region revealed mutant channels with fast current decay at permanent depolarizing pulses above 10mV. It has been previously shown that such a macroscopic inactivation of many Kv7.1 pore mutants occurs in parallel to instantaneous inactivation of Kv7.1 channel. We have chosen four mutant channels I268A, G269A, F339A and F340A with most pronounced current decays to investigate the molecular mechanism underling decay process. Inactivation of these channels could not be explained by intracellular Na+ block reported earlier for Kv7.1 wild type channel. The fast current decay kinetics significantly changed neither by varying the extracellular K+ concentration nor by replacement of the K+ with equimolar Rb+. Recovery from inactivation showed fast and slow components. The slow component was accelerated at high extracellular K+ conditions, whereas the fast component did not change significantly. Our data suggest that instantaneous inactivation of wild type Kv7.1 channel markedly slowed by above mentioned alanine mutations resulting in macroscopic decay of current during prolonged depolarization.

Ozonation of the marine dinoflagellate alga Amphidinium sp.—implications for ballast water disinfection

Ozone has been investigated for its potential to remove marine dinoflagellate algae from ships’ ballast water. Dinoflagellate algae, Amphidinium sp. isolated from the Great Barrier Reef, Townsville, Australia were used as indicators since these produce a type of cyst that is difficult to inactivate, but are relatively easy to culture. The ozonation experiments have demonstrated a high ozone demand for inactivation of the algal cultures, which increases as the culture ages. The main ozone demand in seawater is due to its reaction with bromide to form bromine compounds. The non-bromide ozone demand has been estimated by measuring the residuals produced after various doses of ozone. The Amphidinium sp. show an unexpected response to both ozonation and bromination, with an instantaneous inactivation of the organisms for all doses that produced an oxidant residual in the seawater, followed by an effect of the disinfection residual. The standard design procedure of comparing Ct will not be effective for predicting the response of the organism to varying dose, C , and contact time, t , and a plot of ozone produced oxidant residual against organism inactivation for various contact times is proposed for design purposes. High doses of ozone (5–11 mg/L) and up to 6 h of residual contact were required for a 4-log inactivation of the Amphidinium sp. Ozonation is likely to be a difficult technology to implement for organisms with this ozone requirement in combination with characteristics of ballast tanks, which contain areas of sediments high in detritus and areas of corrosion.

Transposable elements in clonal lineages: lethal hangover from sex

Long-term coevolution of transposable elements (TEs) in sexual hosts leads to evolution of extremely active and dangerous mutagens kept in tenuous check by host-derived mechanisms and via natural selection against TE-rich genomes. To the extent that sexual reproduction and recombination are important in maintaining a stable TE copy number and a tolerable mutation load, the switch to clonality from sexual reproduction can be extremely damaging and, generally, should lead to clonal lineage extinction. Surprisingly however, the loss of powerful selective mechanisms constraining TEs can be beneficial in the short-term by immediately eliminating selective load and possibly promoting the early success of clonal lineages. The clonal lineages that do survive in the long-term must find a way to eliminate or domesticate TEs. Indeed bdelloid rotifers, which are ancient asexuals, do appear to have lost most of the otherwise wide-spread TEs and might have domesticated others. The path to this TE-free haven is anything but clear at the moment. We have considered a novel scenario of instantaneous inactivation of TEs by starting off with a genome carrying repressive host alleles for all TEs in the genome. We show that such a scenario appears plausible and provide some limited empirical evidence in its support.

HIGH PRESSURE INACTIVATION OF PECTIN METHYL ESTERASE IN ORANGE JUICE USING COMBINATION TREATMENTS

The contribution of several high pressure (HP) processing related factors (pressure level, 300-400 MPa; pressure cycle, 1-3, and pressure-hold time, 30–120 min) on the inactivation of pectin methyl esterase (PME) in single strength (pH 3.7 and 11.4 °Brix) and concentrated (pH 3.5 and 42 °Brix) orange juice was evaluated. A response surface methodology was employed to model the combined effects of factors on the enzyme inactivation. The main effects were described by linear or quadratic functions. For both single strength and concentrated orange juices, the effects of all three main factors and some interactions (pressure level, cycle and holding time) were statistically significant (p<0.05). The dual nature of pressure inactivation of PME (with an instantaneous inactivation due to a pressure pulse, instantaneous pressure fall, and first order rate of inactivation during the pressure hold, yielding D and z values) reported in earlier studies was confirmed. Combination models were developed to predict the residual enzyme activity as influenced by the pressure level, number of pressure cycles and pressure hold time.

Optimized Analysis of Intracellular Adenosine and Guanosine Phosphates in Escherichia coli

To investigate the intracellular concentrations of adenosine phosphates in Escherichia coli, especially during bioreactor cultivations, a method that enables reproducible determination of adenosine phosphates in culture solutions containing at least 0.25 g dry cell weight/L has been developed. The detection limits of AMP, ADP, and ATP were found to be as low as 1 pmol. The method involves fast sampling, instantaneous inactivation of cell metabolism, extraction of nucleotides, and quantitative analysis by ion-pair reversed-phase HPLC.

Inactivation of Pectinesterase in Orange and Grapefruit Juices by High Pressure

The enzyme pectinesterase (PE) reduces the quality of citrus juices. Current inactivation of the enzyme is accomplished by heat, resulting in a loss of fresh fruit flavor in the juice. We explored the use of pressurized treatments of orange and grapefruit juices to bypass the use of extreme heat during processing. PE inactivation using isostatic high pressure in the range of 500−900 MPa was accomplished in orange and grapefruit juices. The higher pressures (>600 MPa) caused instantaneous inactivation of the heat labile form of the enzyme but did not inactivate the heat stable form of PE. Treatment times caused significantly different (α = 0.05) total PE activity losses in orange but not in grapefruit juices, and PE inactivation at different pressures was significantly different in both juices. Heat labile grapefruit PE was also more sensitive than orange to pressure. Dp values for orange PE inactivation at 500 and 600 MPa were 83.3 and 2.4 min, respectively; while the zp value between 500 and 600 MPa was ...

Paraquat as a tool for grassland renewal

Three properties of paraquat suggest its use for grassland renewal: rapid absorption into foliage imparting rainfastness, effectiveness against grasses and almost instantaneous inactivation on all but the very lightest of mineral soils. Extensive investigations, both in small plots and on a farm scale under a variety of conditions, have largely confirmed the original promise. Inevitably, in a new development, ancillary techniques are required. In this case new sod seeding methods have been investigated.

THE EFFECT OF VARIOUS CHEMICAL TREATMENTS ON THE ACTIVITY OF THE VIRUSES OF TOMATO SPOTTED WILT AND TOBACCO MOSAIC1

SUMMARYA. Tomato spotted wilt virus (All tests made with suspensions buffered at pH. 7) The concentration of active virus units in suspensions of tomato spotted wilt virus stored at 0oC. in a buffer solution of JJH 7 was maintained without loss for 11 hours by excluding free oxygen. A significant fall in the concentration of active virus units occurred in suspensions treated as in (1) but through which air was bubbled. At room temperatures the virus underwent fairly rapid inactiva‐tion even in the absence of free oxygen, although the presence of oxygen hastened the inactivation. The rate of inactivation in the absence of oxygen varied from time to time, and it is concluded that this inactivation was due to the presence in the infective juice of some oxidized substance which is usually present in only small but variable amounts, and that it is reduced by those substances (see (4) below) which arrest anaerobic inactivation. Certain substances added in the reduced form which yield suspensions with an Eh value of +0–1 volt or less at pH 7 arrested the normal anerobic inactivation of the virus. The remarkable preservative action of cystein is discussed. The virus was rapidly inactivated in vitro by 0–001M solutions of oxidizing agents which induced in the suspensions a potential greater than + 0–2 volt at pH 7. With the exception of methylene blue, oxidizing agents which gave a suspension with an Eh value below +0–1 volt at pH 7 did not inactivate the virus. The reducing agents referred to in (4) protected the virus against inactivation when exposed to air. This protective effect was not permanent but prolonged the activity of inocula for many hours beyond that of the controls. The effect on the virus of a number of other substances was also examined. Those having greatest interest are: (a) KCN, which in 0–01 M solution protected the virus both against anaerobic and‐ aerobic inactivation. Its probable mode of action is discussed on the bases of experiments reported, (b) HgCl2, which in 0.001 M solution caused instantaneous inactivation of the virus, (c) Cathecol, quinol and phenol alone inactivated the virus in the presence of air, but did not do so if Na2SO3 was also present. It is concluded that secondary oxidation products caused the inactivation observed. Attempts to reactivate virus which had been inactivated by exposure to air or by means of HgCl2 were unsuccessful. It has been shown that the inactivating effects observed are due to an action on the virus itself.