Lethality mechanisms in Escherichia coli induced by intense sub-microsecond electrical pulses

In this letter, the authors present the inactivation kinetics of cells of Escherichia coli and its mutants following treatment with high-intensity electrical pulses of 700 and 32 ns durations. Their experimental results suggest that bacterial inactivation by 700 ns pulses is consistent with a mechanism of reversible electroporation, whereas inactivation by 32 ns pulses may occur as a result of damage to intracellular components. They believe that their results represent a first step towards elucidating the mechanism of lethality of submicrosecond pulses of different durations in prokaryotes

Electrode erosion and lifetime performance of a compact and repetitively triggered field distortion spark gap switch

© 1973-2012 IEEE. The electrode erosion and lifetime performance of a compact and repetitively triggered field distortion spark gap switch were studied at a repetitive frequency rate of 30 Hz, a peak current of 8.5 kA, and a working voltage of ±35 kV when the switch was filled with a gas mixture of 30% SF6 and 70% N2 at a pressure of 0.3 MPa. The variations of the time-delay jitter and the self-breakdown voltage were both studied for the whole service lifetime of the spark gap switch. The morphology of both the electrodes and the plate insulator, before and after the service lifetime tests, is also analyzed. The results show that during these tests, the time-delay jitter is basically synchronized with the self-breakdown voltage jitter, and both undergo firstly a process of rapidly decreasing their values, then remaining stable, and finally and gradually increasing after 70 000 pulses. The change in the electrode surface roughness (i.e., surface profile) is caused by erosion and chemical deposits in the switch cavity, which are mainly the two factors that affect the time-delay jitter of the switch. Tip protrusions on the electrode surface, due to electrode erosion, contribute to reducing the time-delay jitter. However, due to chemical reactions, fluorides and sulfides are deposited on the switch components, as well as metal particles caused by electrode erosion sputtering. Slowly, after a large number of shots, all these phenomena affect the self-breakdown performance resulting in an increased self-breakdown voltage jitter, which also causes the time-delay jitter to increase. Although there are a number of reasons that contribute to the deterioration of the performance of the switch, it is fortunate that if a switch suffering a degraded performance is reassembled, with the electrodes mechanically polished and all the components cleaned, the optimal performance of the switch can be restored. If maintenance work is carried out regularly to preserve the condition of the switch's inner components, the service lifetime of the switch can be prolonged

Interaction of Sub-Microsecond Pulsed Electric Field With Bacterial Cells

In the bacterial decontamination of liquid foods, the use of a sub microsecond pulsed electric field is of significant interest because it offers advantages such as negligible thermal effects, superior energy efficiency, and a much-reduced probability of medium breakdown. The reduced pulse duration also affects the mechanism by which sub microsecond pulses inactivate bacterial cells. We provide insight into possible bacterial inactivation mechanisms by sub-microsecond electric pulse with the aid of a common bacterium-wild type Escherichia coli and its mutants. Two pulsed power sources have been designed, developed and tested-one with pulse duration of 32 ns, the other 700 ns, and both are capable of establishing sufficiently high electric field intensity. The experimental results suggest that bacterial inactivation by 700 ns pulses is due to electrical breakdown of the outer cell membrane, whereas inactivation by 32 ns pulses is possibly due to interaction with intracellular structures

The distribution of inverted repeat sequences in the Saccharomyces cerevisiae genome

Although a variety of possible functions have been proposed for inverted repeat sequences (IRs), it is not known which of them might occur in vivo. We investigate this question by assessing the distributions and properties of IRs in the Saccharomyces cerevisiae (SC) genome. Using the IRFinder algorithm we detect 100,514 IRs having copy length greater than 6 bp and spacer length less than 77 bp. To assess statistical significance we also determine the IR distributions in two types of randomization of the S. cerevisiae genome. We find that the S. cerevisiae genome is significantly enriched in IRs relative to random. The S. cerevisiae IRs are significantly longer and contain fewer imperfections than those from the randomized genomes, suggesting that processes to lengthen and/or correct errors in IRs may be operative in vivo. The S. cerevisiae IRs are highly clustered in intergenic regions, while their occurrence in coding sequences is consistent with random. Clustering is stronger in the 3′ flanks of genes than in their 5′ flanks. However, the S. cerevisiae genome is not enriched in those IRs that would extrude cruciforms, suggesting that this is not a common event. Various explanations for these results are considered

Gene Profiling of Mta1 Identifies Novel Gene Targets and Functions

BACKGROUND: Metastasis-associated protein 1 (MTA1), a master dual co-regulatory protein is found to be an integral part of NuRD (Nucleosome Remodeling and Histone Deacetylation) complex, which has indispensable transcriptional regulatory functions via histone deacetylation and chromatin remodeling. Emerging literature establishes MTA1 to be a valid DNA-damage responsive protein with a significant role in maintaining the optimum DNA-repair activity in mammalian cells exposed to genotoxic stress. This DNA-damage responsive function of MTA1 was reported to be a P53-dependent and independent function. Here, we investigate the influence of P53 on gene regulation function of Mta1 to identify novel gene targets and functions of Mta1. METHODS: Gene expression analysis was performed on five different mouse embryonic fibroblasts (MEFs) samples (i) the Mta1 wild type, (ii) Mta1 knock out (iii) Mta1 knock out in which Mta1 was reintroduced (iv) P53 knock out (v) P53 knock out in which Mta1 was over expressed using Affymetrix Mouse Exon 1.0 ST arrays. Further Hierarchical Clustering, Gene Ontology analysis with GO terms satisfying corrected p-value<0.1, and the Ingenuity Pathway Analysis were performed. Finally, RT-qPCR was carried out on selective candidate genes. SIGNIFICANCE/CONCLUSION: This study represents a complete genome wide screen for possible target genes of a coregulator, Mta1. The comparative gene profiling of Mta1 wild type, Mta1 knockout and Mta1 re-expression in the Mta1 knockout conditions define "bona fide" Mta1 target genes. Further extensive analyses of the data highlights the influence of P53 on Mta1 gene regulation. In the presence of P53 majority of the genes regulated by Mta1 are related to inflammatory and anti-microbial responses whereas in the absence of P53 the predominant target genes are involved in cancer signaling. Thus, the presented data emphasizes the known functions of Mta1 and serves as a rich resource which could help us identify novel Mta1 functions

A Distinct Translation Initiation Mechanism Generates Cryptic Peptides for Immune Surveillance

MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance

Altering Chemosensitivity by Modulating Translation Elongation

BACKGROUND: The process of translation occurs at a nexus point downstream of a number of signal pathways and developmental processes. Modeling activation of the PTEN/AKT/mTOR pathway in the Emu-Myc mouse is a valuable tool to study tumor genotype/chemosensitivity relationships in vivo. In this model, blocking translation initiation with silvestrol, an inhibitor of the ribosome recruitment step has been showed to modulate the sensitivity of the tumors to the effect of standard chemotherapy. However, inhibitors of translation elongation have been tested as potential anti-cancer therapeutic agents in vitro, but have not been extensively tested in genetically well-defined mouse tumor models or for potential synergy with standard of care agents. METHODOLOGY/PRINCIPAL FINDINGS: Here, we chose four structurally different chemical inhibitors of translation elongation: homoharringtonine, bruceantin, didemnin B and cycloheximide, and tested their ability to alter the chemoresistance of Emu-myc lymphomas harbouring lesions in Pten, Tsc2, Bcl-2, or eIF4E. We show that in some genetic settings, translation elongation inhibitors are able to synergize with doxorubicin by reinstating an apoptotic program in tumor cells. We attribute this effect to a reduction in levels of pro-oncogenic or pro-survival proteins having short half-lives, like Mcl-1, cyclin D1 or c-Myc. Using lymphomas cells grown ex vivo we reproduced the synergy observed in mice between chemotherapy and elongation inhibition and show that this is reversed by blocking protein degradation with a proteasome inhibitor. CONCLUSION/SIGNIFICANCE: Our results indicate that depleting short-lived pro-survival factors by inhibiting their synthesis could achieve a therapeutic response in tumors harboring PTEN/AKT/mTOR pathway mutations

Produsele forestiere nelemnoase în Republica Moldova: caracteristici și dinamica resurselor [The situation of non-wood forest products sector in Republic of Moldova]

After the proclamation of the independence of the Republic of Moldova, the national forestry fund is constantly growing. At the same time, the harvesting and collection of non-timber forest products (PFNL) was intensified by the forest enterprises under the Moldsilva Agency. Non-timber forest products collected are of plant (fruit, berries, herbs, decorative plants) and animal (fish, snails, honey, wild boar) origin. Over time, forestry sector was in a permanent institutional reforming. At present, Moldsilva agency is the administrative authority of the public administration, empowered to ensure the implementation of state policy and sustainable development in the fields of forestry and hunting. After 1990, the commercial potential of forest fruits and berries decreases, as many fruit plantations have degraded or have been transferred to other land use categories. Because of low wages and difficult manual labor, the number of employees in the forestry sector is steadily decreasing. The largest forested area is concentrated in the center of the country. In the period 2001-2009 the forested area significantly increased, especially in the south of the republic due to the implementation of some European projects. The most non-timber forest products collected are those of medicinal utilisation. Due to the dispersion of the forest fund in small forest tracts, the hunting potential is small. The number and species of animals hunted each year in the forest fund are established by Government Decision, these being the boar (Sus scrofa L.) and the pheasant (Phasianus colchicus L.). The purpose of this research is to present the evolution and the development potential of the non-timber forestry sector in the Republic of Moldova in relation to the institutional changes in the central forest authority. The study has the following objectives: describing the institutional evolution of the central forest authority; analyzing the evolution of the number of employees in the forest branch; distribution and evolution of the national forests as the ground of non wood timber products harvesting; assessing the biological and commercial potential of the sector; analyzing the dynamics of PFNL collection by forest enterprises

Transprocessing: a proposed neurobiological mechanism of psychotherapeutic processing

How does the human brain absorb information and turn it into skills of its own in psychotherapy? In an attempt to answer this question, the authors will review the intricacies of processing channels in psychotherapy and propose the term transprocessing (as in transduction and processing combined) for the underlying mechanisms. Through transprocessing the brain processes multimodal memories and creates reparative solutions in the course of psychotherapy. Transprocessing is proposed as a stage-sequenced mechanism of deconstruction of engrained patterns of response. Through psychotherapy, emotional-cognitive reintegration and its consolidation is accomplished. This process is mediated by cellular and neural plasticity changes