GPU-accelerated parallel image reconstruction strategies for magnetic particle imaging.

OBJECTIVE: Image reconstruction is a fundamental step in Magnetic Particle Imaging (MPI). One of the main challenges is the fact that the reconstructions are computationally intensive and time-consuming, so choosing an algorithm presents a compromise between accuracy and execution time, which depends on the application. This work proposes a method that provides both fast and accurate image reconstructions. Approach. Image reconstruction algorithms were implemented to be executed in parallel in graphics processing units (GPUs) using the CUDA framework. The calculation of the model-based MPI calibration matrix was also implemented in GPU to allow both fast and flexible reconstructions. Main results. The parallel algorithms were able to accelerate the reconstructions by up to about 6, 100 times in comparison to the serial Kaczmarz algorithm executed in the CPU, allowing for real-time applications. Reconstructions using the OpenMPIData dataset validated the proposed algorithms and demonstrated that they are able to provide both fast and accurate reconstructions. The calculation of the calibration matrix was accelerated by up to about 37 times. Significance. The parallel algorithms proposed in this work can provide single-frame MPI reconstructions in real time, with frame rates greater than 100 frames per second. The parallel calculation of the calibration matrix can be combined with the parallel reconstruction to deliver images in less time than the serial Kaczmarz reconstruction, potentially eliminating the need of storing the calibration matrix in the main memory, and providing the flexibility of redefining scanning and reconstruction parameters during execution.

TLS Protocol Analysis Using IoTST-An IoT Benchmark Based on Scheduler Traces.

The Internet of Things (IoT) envisions billions of everyday objects sharing information. As new devices, applications and communication protocols are proposed for the IoT context, their evaluation, comparison, tuning and optimization become crucial and raise the need for a proper benchmark. While edge computing aims to provide network efficiency by distributed computing, this article moves towards sensor nodes in order to explore efficiency in the local processing performed by IoT devices. We present IoTST, a benchmark based on per-processor synchronized stack traces with the isolation and precise determination of the introduced overhead. It produces comparable detailed results and assists in determining the configuration that has the best processing operating point so that energy efficiency can also be considered. On benchmarking applications which involve network communication, the results can be influenced by the constant changes that occur in the state of the network. In order to circumvent such problems, different considerations or assumptions were used in the generalization experiments and the comparison to similar studies. To present IoTST usage on a real problem, we implemented it on a commercial off the-shelf (COTS) device and benchmarked a communication protocol, producing comparable results that are unaffected by the current network state. We evaluated different Transport-Layer Security (TLS) 1.3 handshake cipher suites at different frequencies and with various numbers of cores. Among other results, we could determine that the selection of a specific suite (Curve25519 and RSA) can improve the computation latency by up to four times over the worst suite candidate (P-256 and ECDSA), while both providing the same security level (128 bits).

Artificial Intelligence of Things Applied to Assistive Technology: A Systematic Literature Review.

According to the World Health Organization, about 15% of the world's population has some form of disability. Assistive Technology, in this context, contributes directly to the overcoming of difficulties encountered by people with disabilities in their daily lives, allowing them to receive education and become part of the labor market and society in a worthy manner. Assistive Technology has made great advances in its integration with Artificial Intelligence of Things (AIoT) devices. AIoT processes and analyzes the large amount of data generated by Internet of Things (IoT) devices and applies Artificial Intelligence models, specifically, machine learning, to discover patterns for generating insights and assisting in decision making. Based on a systematic literature review, this article aims to identify the machine-learning models used across different research on Artificial Intelligence of Things applied to Assistive Technology. The survey of the topics approached in this article also highlights the context of such research, their application, the IoT devices used, and gaps and opportunities for further development. The survey results show that 50% of the analyzed research address visual impairment, and, for this reason, most of the topics cover issues related to computational vision. Portable devices, wearables, and smartphones constitute the majority of IoT devices. Deep neural networks represent 81% of the machine-learning models applied in the reviewed research.

POEMS Syndrome Diagnosis in a Patient with Mixed Polyneuropathy: Case Report.

POEMS syndrome is a rare condition of paraneoplasic origin characterized by the presence of a sensorimotor polyneuropathy associated with the presence of a proliferative disorder of plasmatic monoclonal cells and overproduction of vascular endothelial growth factor. The acronym "POEMS" represents multisystem findings including polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes; nevertheless, clinical presentation is heterogeneous. We describe a clinical case, the diagnostic and therapeutic approach in a patient with sensorimotor polyneuropathy in whom POEMS syndrome was diagnosed; to understand this pathology, its clinical and paraclinical manifestations in order to make a diagnosis or to avoid a delayed one and to provide an adequate treatment.

Redox stress response and UV tolerance in the acidophilic iron-oxidizing bacteria Leptospirillum ferriphilum and Acidithiobacillus ferrooxidans.

The oxidative stress response represents a sum of antioxidative mechanisms that are essential for determining the adaptation and abundance of microorganisms in the environment. Leptospirillum ferriphilum and Acidithiobacillus ferrooxidans are chemolithotrophic bacteria that obtain their energy from the oxidation of ferrous ion. Both microorganisms are important for bioleaching of sulfidic ores and both are tolerant to high levels of heavy metals and other factors that can induce oxidative stress. In this work, we compared the tolerance and response of L. ferriphilum and At. ferrooxidans to Fe3+, H2O2, K2CrO4, and UV-C radiation. We evaluated growth, generation of reactive oxygen species (ROS), oxidative damage to lipid membranes and DNA, and the activity of antioxidative proteins in cells exposed to these stressors. L. ferriphilum had higher cell density, lower ROS content and less lipid and DNA damage than At. ferrooxidans. Consistent with this, the activity levels of thioredoxin and superoxide dismutase in L. ferriphilum were upregulated and higher than in At. ferrooxidans. This indicated that L. ferriphilum has a higher capacity to respond to oxidative stress and to manage redox homeostasis. This capacity could largely contribute to the high abundance of this species in natural and anthropogenic sites.

Virtual Reality Applied in a Thermoelectric Power Plant Planning

Abstract The planning of a new thermal power plant is linked to the various decision elements and evaluation criteria. Factors such as the plant's geographic positioning, primary energy supply points, paths, and means of delivery of this primary energy should be analyzed. Similar studies are imposed when studying the change of a thermoelectric plant's primary energy source occurs. In Brazil, several plants are currently investigating the exchange of their primary fuel from oil to gas due to the decrees issued by ANEEL. This paper presents software, which uses virtual reality to assist in the various stages of the planning process and in the analyses that must be performed. This software was developed for the Hidrotermica Group and had as the primary target the Borborema Thermoelectric Power Plant.

Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells.

Thyroid hormones (THs) - 3,3',5-triiodo-L-thyronine (T3) and L-thyroxine (T4) - are important regulators of the metabolism and physiology of most normal tissues. Cytochrome P450 family 3A members are drug metabolizing enzymes involved in the activation and detoxification of several drugs. CYP3A4 is the major enzyme involved in the metabolism of chemotherapeutic drugs. In this work, we demonstrate that THs induce a significant increase in CYP3A4 mRNA levels, protein expression and metabolic activity through the membrane receptor integrin αvß3 and the activation of signalling pathways through Stat1 and NF-κB. We reasoned that TH-induced CYP3A4 modulation may act as an important regulator in the metabolism of doxorubicin (Doxo). Experiments in vitro demonstrated that in CYP3A4-knocked down cells, no TH-mediated chemosensitivity to Doxo was observed. We also found that THs modulate these functions by activating the membrane receptor integrin αvß3. In addition, we showed that the thyroid status can modulate CYP450 mRNA levels in tumor and liver tissues, and the tumor volume in response to chemotherapy in vivo. In fact, Doxo treatment in hypothyroid mice was associated with lower tumors, displaying lower levels of CYP enzymes, than euthyroid mice. However, higher mRNA levels of CYP enzymes were found in livers from Doxo treated hypothyroid mice respect to control. These results present a new mechanism by which TH could modulate chemotherapy response. These findings highlight the importance of evaluating thyroid status in patients during application of T-cell lymphoma therapeutic regimens.

Morte súbita cardíaca: perfil epidemiológico na região metropolitana de Goiânia / Sudden cardiac death: epidemiological profile in the metropolitan area of Goiania

Introdução: A morte súbita cardíaca é um evento de grande importância e repercussão na saúde pública e se configura como a manifestação mais letal de uma doença cardíaca. Este estudo teve como objetivo traçar as características da morte súbita cardíaca na região metropolitana de Goiânia (GO).Método: O presente estudo analisou 2.681 relatórios completos de necropsia, dos quais 314 foram selecionados como morte súbita cardíaca.Foram coletados dados como sexo das vítimas, faixa etária, local e horário do óbito, presença de tabagismo, além das comorbidades hipertensão arterial sistêmica, diabetes melito, dislipidemia e histórico de doença de Chagas. Resultados: Dos 314 casos de morte súbita cardíaca, os mais acometidos foram homens, entre a sexta e a sétima décadas de vida. O local em que houve mais casos foi o domicílio, ocorrendo a maioria no período matutino. A hipertensão foi a comorbidade mais prevalente, com alta proporção (58,9%). Mais de 10% dos pacientes apresentavam histórico de doença de Chagas. Conclusão: Percebe-se a importância de um maior entendimento da morte súbita cardíaca dentro da realidade da região metropolitana estudada. Entender o perfil epidemiológico local é um passo fundamental para que estratégias preventivas sejam implementadas pelas lideranças políticas

Background: Sudden cardiac death is an important event which has an impact on public health and is the most lethal manifestation of heart disease. This study is aimed at describing the characteristics of sudden cardiac death in the metropolitan area of Goiania (GO). Methods: This study examined 2,681 necropsy reports of which 314 were selected as sudden cardiac death. Data such as gender, age, location and time of death, presence of smoking, comorbidities such as hypertension, diabetes mellitus, dyslipidemia and Chagas disease history were collected. Results: Among 314 cases of sudden cardiac death, the most affected patients were males, between 60 and 70 years of age. The most common location for the event was the patient's own house, and most of them occurred in the morning. Hypertension was the most prevalent comorbidity, with a high incidence (58.9%). More than 10% of the patients had a history of Chagas disease. Conclusion: A better understanding of sudden cardiac death in the metropolitan area should be further studied. Understanding the local epidemiological profile is a crucial step towards the development of preventive strategies that must be implemented by political leaders

Obesidad y cáncer: fisiopatología y evidencia epidemiológica / Obesity and cancer: pathophysiology and epidemiological evidence

Introducción: La obesidad es reconocida como un importante problema de salud pública en todo el mundo, la prevalencia de sobrepeso y obesidad está aumentando a un ritmo alarmante tanto en países desarrollados como en vía de desarrollo, tanto así, que la obesidad ha sido considerada como la epidemia del siglo XXI. El exceso de peso corporal es un factor de riesgo importante en la aparición de enfermedades crónicas y determinados tipos de cáncer, tales como el cáncer de colon, mama en mujeres menopáusicas, endometrio, riñón y cáncer de esófago. Métodos: En junio del 2015, se realizó una búsqueda sistemática de la literatura científica en las principales bases de datos biomédicas: PUBMED, EMBASE, MEDLINE, LILACS, IMBIOMED, COCHRANE, entre el año 1980 y 2015. Utilizando las siguientes palabras clave: cáncer, obesidad, neoplasia, sobrepeso, epidemiologia, asociación y revisión. Resultados: se encontró que existe una asociación estadísticamente significativa entre la obesidad y diversos tipos de cáncer, tales como el cáncer de colon, de mama en mujeres posmenopáusico, de endometrio, de riñón, y de esófago. La obesidad y el sobrepeso pueden tener efectos notables sobre varios sistemas fisiológicos que pueden posteriormente aumentar el riesgo de cáncer. Conclusión: Existe una asociación entre la obesidad y la aparición de diversostipos de cáncer, la comprensión de los mecanismos causales de esta asociaciónes importante para la implementación de medidas de salud pública y cambiosen el estilo de vida, que busquen prevenir la aparición del cáncer y la obesidad.

Integrin αvß3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells.

The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvß3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin αvß3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvß3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin αvß3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvß3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.

Thyroid hormones-membrane interaction: reversible association of hormones with organized phospholipids with changes in fluidity and dipole potential.

Differential scanning calorimetry (DSC), mixed monomolecular layers and fluorescence spectroscopy techniques were applied to investigate the effect of thyroid hormones (THs) on the biophysical properties of model membranes. We found that both 3,3',5-triiodo-L-thyronine (T3) and 3,5,3',5'-tetraiodo-L-thyronine (T4) induce a broadening of the calorimetric main phase transition profile and reduce the transition enthalpy in liquid-crystalline state of dipalmitoylphosphatylcholine (DPPC) multilamellar vesicles. Tm changes from 41 °C to 40 °C compared to pure DPPC. When the experiments were done by adding THs to preformed multilamellar vesicles a second broader component in the DSC scan also appears at 20 min of incubation and becomes gradually more prominent with time, indicating a progressive alteration of lipid phase induced by THs. Analysis of surface pressure-molecular area isotherms in mixed monolayers of THs with either DPPC or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) at air-water interface indicated a reduction in molecular area for THs/lipid mixtures at all surface pressures. A substantial decrease in surface potential in mixed lipid/THs monolayers at all surface pressures were observed for both phospholipids without affecting the mixed monolayer integrity. The data of mixed lipid/THs behavior support the establishment of lateral miscibility. Alterations of bidimensional liquid expanded→liquid condensed phase transition observed for DPPC/THs mixed monolayers are compatible with the changes observed in DSC. The transverse movement of THs and the decrease of dipole potential were also observed in single unilamellar vesicles by using appropriate fluorescent probes.

Macrophage environment turns otherwise MccJ25-resistant Salmonella into sensitive.

BACKGROUND: Microcin J25 (MccJ25) is a plasmid-encoded antibiotic peptide produced by Escherichia coli (E. coli). MccJ25 enters into the sensitive E. coli strains by the outer membrane receptor FhuA and the inner membrane proteins TonB, ExbB, ExbD and SbmA. The resistance of Salmonella enterica serovar Typhimurium (S. Typhimurium) to MccJ25 is attributed to the inability of its FhuA protein to incorporate the antibiotic into the cell. RESULTS: In this work we demonstrate that S. Typhimurium becomes notably susceptible to MccJ25 when replicating within macrophages. In order to determine the possible cause of this phenomenon, we studied the sensitivity of S. Typhimurium to MccJ25 at conditions resembling those of the internal macrophage environment, such as low pH, low magnesium and iron deprivation. We observed that the strain was only sensitive to the antibiotic at low pH, leading us to attribute the bacterial sensitization to this condition. A MccJ25-resistant E. coli strain in which fhuA is deleted was also inhibited by the antibiotic at low pH. Then, we could assume that the MccJ25 sensitivity change observed in both E. coli fhuA and S. Typhimurium is mediated by a MccJ25 uptake independent of the FhuA receptor. Moreover, low pH incubation also sensitized S. Typhimurium to the hydrophobic antibiotic novobiocin, which does not affect enteric bacteria viability because it is unable to penetrate the bacterial outer membrane. This observation supports our hypothesis about low pH producing a modification in the bacterial membrane permeability that allows an unspecific MccJ25 uptake. On the other hand, MccJ25 inhibited S. Typhimurium when cells were preincubated in acidic pH medium and then treated at neutral pH with the antibiotic. CONCLUSIONS: Our results suggest that acidic condition does not alter MccJ25 hydrophobicity but irreversibly modifies bacterial membrane permeability. This would allow an unspecific antibiotic uptake into the cell.From our data it is possible to infer that intracellular pathogenic strains, which are in vitro resistant to MccJ25, could become susceptible ones in vivo. Therefore, the MccJ25 action spectrum would be broader than what in vitro experiments indicate.

Prevalence assessment of root dilaceration in permanent incisors

INTRODUCTION: Root dilaceration is a dental anomaly characterized by an abnormal curvature of the dental root, which can cause problems during eruption and complications in the orthodontic and endodontic treatment or extraction. OBJECTIVE: The aim of this study was to determine the prevalence of root dilaceration in permanent incisors in an oral radiology clinic in the city of João Pessoa / PB, Brazil. METHODS: The sample consisted of 548 patients who allowed assessments of their dental radiographs, a total of 3,948 examined teeth. Each tooth was examined according to the occurrence of root dilaceration, regarding type (mild, moderate or severe), root third that it was in and direction of the root. The angle formed by the root deviation in relation to the long tooth axis was obtained by means of a diagram printed on transparent acetate, placed over the radiograph. RESULTS: The results were analyzed with SPSS software (Statistical Package for Social Sciences) version 13.0, performing an exploratory data analysis. The prevalence of root dilaceration in the studied sample was 1.03% (41 cases), with higher incidence in males (65.8%), being the superior lateral incisor the most affected teeth (78%). The most prevalent type of root dilaceration was the mild one (73.1%), occurring more in the apical third (90.2%) and with distal direction of the root (95.1%). CONCLUSION: Considering these results, it is emphasized the importance of performing a diagnostic radiographic examination prior to planning a treatment in permanent anterior teeth.

INTRODUÇÃO: a dilaceração radicular é uma anomalia dentária caracterizada por uma curvatura anormal na raiz do dente que pode causar problemas na erupção e complicações durante movimentação ortodôntica, tratamento endodôntico ou exodontia. OBJETIVO: o objetivo do presente trabalho foi verificar a prevalência da dilaceração radicular em incisivos permanentes, em uma clínica de radiologia odontológica da cidade de João Pessoa/PB. MÉTODO: a amostra foi constituída de 548 pacientes que possibilitaram avaliações em suas radiografias dentárias, totalizando 3948 dentes examinados. Examinou-se cada dente segundo a ocorrência de dilaceração radicular, com relação ao tipo (discreta, moderada ou severa), o terço radicular em que se encontrava e a direção da raiz. A angulação formada pelo desvio da raiz em relação ao longo eixo do dente foi obtida por meio de um diagrama impresso em acetato transparente, colocado sobre a radiografia. RESULTADOS: os resultados foram analisados no programa SPSS, efetuando-se uma análise exploratória dos dados. A prevalência da dilaceração radicular na amostra estudada foi de 1,03% (41 casos), com maior incidência no sexo masculino (65,8%), sendo os incisivos laterais superiores os dentes mais acometidos (78%). O tipo de dilaceração radicular mais prevalente foi a discreta (73,1%), ocorrendo mais no terço apical (90,2%) e com direção distal da raiz (95,1%). CONCLUSÃO: diante desses resultados, ressaltam-se a importância da realização prévia de um exame radiográfico de diagnóstico ao planejar um tratamento em dentes permanentes anteriores.

Cu(II)-reduction by Escherichia coli cells is dependent on respiratory chain components.

Copper is both an essential nutrient and a toxic element able to catalyze free radicals formation which damage lipids and proteins. Although the available copper redox species in aerobic environment is Cu(II), proteins that participate in metal homeostasis use Cu(I). With isolated Escherichia coli membranes, we have previously shown that electron flow through the respiratory chain promotes cupric ions reduction by NADH dehydrogenase-2 and quinones. Here, we determined Cu(II)-reductase activity by whole cells using strains deficient in these respiratory chain components. Measurements were done by the appearance of Cu(I) in the supernatants of cells exposed to sub-lethal Cu(II) concentrations. In the absence of quinones, the Cu(II)-reduction rate decreased ~70% in respect to the wild-type strain, while this diminution was about 85% in a strain lacking both NDH-2 and quinones. The decrease was ~10% in the absence of only NDH-2. In addition, we observed that quinone deficient strains failed to grow in media containing either excess or deficiency of copper, as we have described for NDH-2 deficient mutants. Thus, the Cu(II)-reduction by E. coli intact cells is mainly due to quinones and to a lesser extent to NDH-2, in a quinone-independent way. To our knowledge, this is the first in vivo demonstration of the involvement of E. coli respiratory components in the Cu(II)-reductase activity which contributes to the metal homeostasis.

Redox-active tyrosine residue in the microcin J25 molecule.

Microcin J25 (MccJ25) is a 21 amino acid lasso-peptide antibiotic produced by Escherichia coli and composed of an 8-residues ring and a terminal 'tail' passing through the ring. We have previously reported two cellular targets for this antibiotic, bacterial RNA polymerase and the membrane respiratory chain, and shown that Tyr9 is essential for the effect on the membrane respiratory chain which leads to superoxide overproduction. In the present paper we investigated the redox behavior of MccJ25 and the mutant MccJ25 (Y9F). Cyclic voltammetry measurements showed irreversible oxidation of both Tyr9 and Tyr20 in MccJ25, but infrared spectroscopy studies demonstrated that only Tyr9 could be deprotonated upon chemical oxidation in solution. Formation of a long-lived tyrosyl radical in the native MccJ25 oxidized by H2O2 was demonstrated by Electron Paramagnetic Resonance Spectroscopy; this radical was not detected when the reaction was carried out with the MccJ25 (Y9F) mutant. These results show that the essential Tyr9, but not Tyr20, can be easily oxidized and form a tyrosyl radical.

Cooperative nongenomic and genomic actions on thyroid hormone mediated-modulation of T cell proliferation involve up-regulation of thyroid hormone receptor and inducible nitric oxide synthase expression.

Thyroid hormones (THs) exert a broad range of actions on development, growth, and cell differentiation by both genomic and nongenomic mechanisms. THs regulate lymphocyte function, but the participation of nongenomic actions is still unknown. Here the contribution of both genomic and nongenomic effects on TH-induced division of T cells was studied by using free and noncell permeable THs coupled to agarose (TH-ag). THs-ag led to cell division, but to a lesser extent than free hormones. THs induced nongenomically the rapid translocation of protein kinase C (PKC) ζ isoform to cell membranes, extracellular-signal-regulated kinases (ERK1/2) phosphorylation and nuclear factor-κB (NF-κB) activation. The signaling cascade include sphingomyelinases acting up-stream the activation of PKCζ isoform, while ERK and NF-κB are activated downstream this PKC isoenzyme. Both free and THs-ag increased the protein and mRNA levels of TH nuclear receptor TRα1, while only free hormones incremented the inducible NOS gene and protein levels as well as a calcium independent NOS activity. Both effects were blunted by PKCζ inhibition. These results indicate that THs, by triggering a nongenomic signaling cascade that involves Smases-mediated activation of PKCζ, lead to ERK 1/2 and NF-κB activation and to the genomic increase of TRs and the inducible nitric oxide synthase protein and mRNA levels, improving T lymphocyte proliferation. These finding not only contribute to the understanding of the mechanisms involved in TH modulation of lymphocyte physiology, but would also point out for the first time the interplay between genomic and nongenomic TH actions in T cells.

Sensitization of microcin J25-resistant strains by a membrane-permeabilizing peptide.

Microcin J25 (MccJ25) is a plasmid-encoded, 21-amino-acid, antibacterial peptide produced by Escherichia coli. MccJ25 inhibits RNA polymerase and the membrane respiratory chain. MccJ25 uptake into E. coli-sensitive strains is mediated by the outer membrane receptor FhuA and the inner membrane proteins TonB, ExbB, ExbD, and SbmA. This peptide is active on some E. coli, Salmonella, and Shigella species strains, while other Gram-negative bacteria, such as clinical isolates of Enterobacter cloacae, Citrobacter freundii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Moraxella catarrhalis, and Salmonella enterica serovar Typhimurium, are completely resistant. In the present work, we demonstrated that the membrane-permeabilizing peptide (KFF)3K made some resistant strains sensitive to MccJ25, among them S. Typhimurium, where the antibiotic inhibits in vitro cell growth and bacterial replication within macrophages. The results demonstrate that the membrane permeabilization induced by (KFF)3K allows MccJ25 penetration in an FhuA and SbmA-independent manner and suggest that the combination of both peptides could be considered as a therapeutic agent against pathogenic Salmonella strains.

Glyceraldehyde-3-phosphate dehydrogenase tetramer dissociation and amyloid fibril formation induced by negatively charged membranes.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme related with Huntington's, Parkinson's and Alzheimer's diseases. The ability of negatively charged membranes to induce a rapid formation of GAPDH amyloid fibrils has been demonstrated, but the mechanisms by which GAPDH reaches the fibrillar state remains unclear. In this report, we describe the structural changes undergone by GAPDH at physiological pH and temperature conditions right from its interaction with acidic membranes until the amyloid fibril is formed. According to our results, the GAPDH-membrane binding induces a beta-structuring process along with a loss of quaternary structure in the enzyme. In this way, experimental evidences on the initial steps of GAPDH amyloid fibrils formation pathway are provided.

Tyrosine 9 is the key amino acid in microcin J25 superoxide overproduction.

Escherichia coli microcin J25 (MccJ25) is a lasso-peptide antibiotic comprising 21 L-amino acid residues (G(1)-G-A-G-H(5)-V-P-E-Y-F(10)-V-G-I-G-T(15)-P-I-S-F-Y(20)-G). MccJ25 has two independent substrates: RNA-polymerase (RNAP) and the membrane respiratory chain. The latter is mediated by oxygen consumption inhibition together with an increase of superoxide production. In the present paper, the antibiotic MccJ25 was engineered by substituting Tyr(9) or Tyr(20) with phenylalanine. Both mutants were well transported into the cells and remained active on RNAP. Only the Y9F mutant lost the ability to overproduce superoxide and inhibit oxygen consumption. The last results confirm that the Tyr(9), and not Tyr(20), is involved in the MccJ25 action on the respiratory chain target.

Potential applicability of chymotrypsin-susceptible microcin J25 derivatives to food preservation.

Microcin J25 (MccJ25) is a 21-residue ribosomally synthesized lariat peptide antibiotic. MccJ25 is active against such food-borne disease-causing pathogens as Salmonella spp., Shigella spp., and Escherichia coli, including E. coli O157:H7 and non-O157 strains. MccJ25 is highly resistant to digestion by proteolytic enzymes present in the stomach and intestinal contents. MccJ25 would therefore remain active in the gastrointestinal tract, affecting normal intestinal microbiota, and this limits the potential use of MccJ25 as a food preservative. In the present paper, we describe a chymotrypsin-susceptible MccJ25 derivative with a mutation of Gly(12) to Tyr that retained almost full antibiotic activity and efficiently inhibited the growth of pathogenic Salmonella enterica serovar Newport and Escherichia coli O157:H7 in skim milk and egg yolk. However, unlike the wild-type MccJ25, the MccJ25(G12Y) variant was inactivated by digestive enzymes both in vitro and in vivo. To our knowledge, our results represent the first example of a rational modification of a microcin aimed at increasing its potential use in food preservation.