Prevalencia y severidad de Hiponatremias en niños internados en el Hospital Pediátrico: estudio de cohorte / Prevalence and severity of hyponatremia in children admitted to a pediatric hospital: a cohort study

Introducción: Para disminuir la aparición de hiponatremias en los últimos años se aumentaron las concentraciones de sodio en las soluciones de mantenimiento, llegando a recomendarse las isotónicas, con mejoras de laboratorio pero con dudoso impacto clínico. En el Hospital Garrahan se utiliza una solución estándar hipotónica con cloruro de sodio 0,45%. Antes de reemplazar la solución según recomendaciones internacionales se decidió establecer la prevalencia de hiponatremia en pacientes internados, y su asociación con la solución estándar de hidratación. Población y métodos: Pacientes de 1 mes a 18 años, internados en el Hospital Garrahan. Estudio prospectivo y observacional. Se registró si el paciente recibía hidratación parenteral y la concentración de sodio. Se consideró hiponatremia significativa la presencia de sodio sérico menor a 130 mEq/L. y/o la presencia de síntomas compatibles con hiponatremia. Resultados: En 3003 internaciones la prevalencia global de hiponatremias diagnosticadas fue 4.4%, y asciende a 6.3% si se consideran solo los pacientes que fueron estudiados con ionograma (se le extrajo ionograma al 70,6% de los pacientes internados). La prevalencia de hiponatremias significativas fue de 1.5% (n=44) de los internados, y las hiponatremias significativas en internados que recibían la solución hipotónica estándar de mantenimiento fue de 0.3% (n=9). Conclusiones: En una población donde se utiliza una solución estándar con cloruro de sodio 0,45% -pero se modifica individualmente para las necesidades de cada paciente- la prevalencia de hiponatremias totales y significativas fue similar e incluso inferior a la publicada en otras series. (AU)

Introduction: To reduce the appearance of hyponatremia, in recent years, sodium concentrations were increased in maintenance solutions, and isotonic solutions were recommended, leading to improvements in laboratory studies, but with a doubtful clinical impact. A standard hypotonic solution with 0.45% sodium chloride is used at Garrahan Hospital. Before replacing the solution according to international recommendations, it was decided to determine the prevalence of hyponatremia in inpatients and its association with the standard hydration solution. Population and methods: Patients from 1 month to 18 years old, hospitalized at Garrahan Hospital. Prospective and observational study. Parenteral hydration of the patient and the sodium concentration were recorded. Significant hyponatremia was defined as serum sodium less than 130 mEq/L, and/or the presence of symptoms of hyponatremia. Results: In 3003 hospitalizations, the overall prevalence of diagnosed hyponatremia was 4.4%, increasing to 6.3% if only patients in whom a ionogram was performed were included (a ionogram was performed in 70.6% of the inpatients). Of all inpatients, 1.5% (n=44) had significant hyponatremia, and 0.3% (n=9) of the patients receiving the standard maintenance hypotonic solution had significant hyponatremia. Conclusions: In a population in whom a standard solution with 0.45% sodium chloride is used - but which is individually modified according to the needs of each patient - the prevalence of total and significant hyponatremia was similar and even lower than that reported in other series (AU)

Cellular and Acellular Assays for Measuring Oxidative Stress Induced by Ambient and Laboratory-Generated Aerosols.

INTRODUCTION: Many studies have established associations between exposure to air pollution, or atmospheric particulate matter (PM), and adverse health effects. An increasing array of studies have suggested oxidative stress as a possible mechanism by which PM-induced health effects arise, and as a result, many chemical and cellular assays have been developed to study PM-induced oxidant production. Although significant progress has been made in recent years, there are still many gaps in this area of research that have not been addressed. Many prior studies have focused on the aerosol of primary origin (e.g., the aerosol emitted from combustion engines) although the aerosol formed from the oxidation of volatile species, secondary organic aerosol (SOA), has been shown to be the predominant type of aerosol even in urban areas. Current SOA health studies are limited in number, and as such, the health effects of SOA are poorly characterized. Also, there is a lack of perspective in terms of the relative toxicities of different SOA systems. Additionally, although chemical assays have identified some SOA constituents associated with adverse health endpoints, the applicability of these results to cellular responses has not been well established. SPECIFIC AIMS: The overall objective of this study was to better understand the oxidative properties of different types and components of PM mixtures (especially SOA) through systematic laboratory chamber experiments and ambient field studies. The study had four specific aims.1 To develop a cellular assay optimized for measuring reactive oxygen and nitrogen species (ROS/RNS) production resulting from PM exposure and to identify a robust parameter that could represent ROS/RNS levels for comparison with different endpoints.2 To identify ambient PM components associated with ROS/RNS production and evaluate whether results from chemical assays represented cellular responses in terms of ROS/RNS production.3 To investigate and provide perspective on the relative toxicities of SOA formed from common biogenic and anthropogenic precursors under different conditions (e.g., humidity, nitrogen oxides [NOx], and redox-active metals) and identify bulk aerosol properties associated with cellular responses.4 To investigate the effects of photochemical aging on aerosol toxicity. METHODS: Ambient PM samples were collected from urban and rural sites in the greater Atlanta area as part of the Southeastern Center for Air Pollution and Epidemiology (SCAPE) study between June 2012 and October 2013. The concentrations of water-soluble species (e.g., water-soluble organic carbon [WSOC], brown carbon [Br C], and metals) were characterized using a variety of instruments. Samples for this study were chosen to span the observed range of dithiothreitol (DTT) activities.Laboratory studies were conducted in the Georgia Tech Environmental Chamber (GTEC) facility in order to generate SOA under well-controlled photooxidation conditions. Precursors of biogenic origin (isoprene, α-pinene, and ß-caryophyllene) and anthropogenic origin (pentadecane, m-xylene, and naphthalene) were oxidized under various formation conditions (dry vs. humid, NOx, and ammonium sulfate vs. iron sulfate seed particles) to produce SOA of differing chemical composition and mass loading. For the naphthalene system, a series of experiments were conducted with different initial hydrocarbon concentrations to produce aerosols with various degree of oxidation. A suite of instruments was utilized to monitor gas- and particle-phase species. Bulk aerosol properties (e.g., O:C, H:C, and N:C ratios) were measured using a high-resolution time-of-flight aerosol mass spectrometer. Filter samples were collected for chemical oxidative potential and cellular measurements. For the naphthalene system, multiple filter samples were collected over the course of a single experiment to collect aerosols of different photochemical aging.For all filter samples, chemical oxidative potentials were determined for water-soluble extracts using a semiautomated DTT assay system. Murine alveolar macrophages and neonatal rat ventricular myocytes were also exposed to PM samples extracted in cell culture medium to investigate cellular responses. ROS/RNS production was detected using the intracellular ROS/RNS probe, carboxy-2',7'-dichlorodihydrofluorescein diacetate (carboxy-H2DCFA), whereas cellular metabolic activity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Finally, cytokine production, that is, secreted levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were measured post-exposure using an enzyme-linked immunosorbent assay (ELISA). To identify PM constituents associated with oxidative properties, linear regressions between oxidative properties (cellular responses or DTT activity) and aerosol composition (metals, elemental ratios, etc.) were evaluated using Pearson's correlation coefficient, where the significance was determined using multiple imputation and evaluated using a 95% confidence interval. RESULTS: We optimized several parameters for the ROS/RNS assay, including cell density (2 × 104 cells/well for macrophages and 3.33 × 104 cells/well for cardiomyocytes), probe concentration (10 µM), and sample incubation time (24 hours). Results from both ambient and laboratory-generated aerosols demonstrate that ROS/RNS production was highly dose-dependent and nonlinear with respect to PM dose. Of the dose-response metrics investigated in this study (maximum response, dose at which the response is 10% above the baseline [threshold], dose at which 50% of the response is attained [EC50], rate at which the maximum response is attained [Hill slope], and area under the dose-response curve [AUC]), we found that the AUC was the most robust parameter whose informativeness did not depend on dose range.A positive, significant correlation was observed between ROS/RNS production as represented by AUC and chemical oxidative potential as measured by DTT for ambient samples collected in summer. Conversely, a relatively constant AUC was observed for ambient samples collected in winter regardless of the corresponding DTT activity. We also identified several PM constituents (WSOC, BrC, iron, and titanium) that were significantly correlated with AUC for summer samples. The strong correlation between organic species and ROS/RNS production highlights a need to understand the contribution of organic aerosols to PM-induced health effects. No significant correlations were observed for other ROS/RNS metrics or PM constituents, and no spatial trends were observed.For laboratory-generated aerosol, precursor identity influenced oxidative potentials significantly, with isoprene and naphthalene SOA having the lowest and highest DTT activities, respectively. Both precursor identity and formation condition significantly influenced inflammatory responses induced by SOA exposure, and several response patterns were identified for SOA precursors whose photooxidation products share similar carbon-chain length and functionalities. The presence of iron sulfate seed particles did not have an apparent effect on oxidative potentials; however, a higher level of ROS/RNS production was observed for all SOA formed in the presence of iron sulfate compared with ammonium sulfate. We also identified a significant positive correlation between ROS/RNS production and average carbon oxidation state, a bulk aerosol property. It may therefore be possible to roughly estimate ROS/RNS production using this property, which is readily obtainable. This correlation may have significant implications as aerosols have an atmospheric lifetime of a week, during which average carbon oxidation state increases because of atmospheric photochemical aging. Our results suggest that aerosols might become more toxic as they age in the atmosphere. Finally, in the context of ambient samples, laboratory-generated SOA induced comparable or higher levels of ROS/RNS. Oxidative potentials for all laboratory SOA systems, with the exception of naphthalene (which was higher), were all comparable with oxidative potentials observed in ambient samples.

[Low-risk community-acquired pneumonia: implications of its outcome due to the determining factors for admission not contemplated by the scores]. / Neumonía adquirida en la comunidad de bajo riesgo: Consecuencias evolutivas de los determinantes de internación no contemplados por los scores.

OBJECTIVES: The decision to admit patients with community-acquired pneumonia (CAP) to hospital are based on stratification scales. This classification into risk groups is not perfect. In low-risk community-acquired pneumonia (LR-CAP), physicians often depend on their subjective impressions to decide the need for hospitalisation, which suggests the existence of conditions not considered by the scores. The aim of this article was to describe the determining factors for admission in LR-CAP, and to analyse the relationship between these causes and clinical outcome. MATERIAL AND METHODS: A descriptive, observational, retrospective study, based on the review of medical records during a 2 year-period. It included patients over 18 years, who were hospitalised in a third level hospital in Argentina due to LR-CAP. RESULTS: A total of 80 cases were identified. The causes that led to hospitalisation were: comorbidities not included in the scores, development of pleural effusion and sepsis, lack of response to ambulatory antibiotic treatment, oral intolerance, and social causes. HIV infection was associated with an unfavourable clinical progress during hospital admission (p=.03), as well as the lack of response to outpatient treatment (p=.03) and the development of pleural effusion (p=.03). Social causes were associated with a need for longer intravenous treatment. CONCLUSIONS: HIV infection, social causes, and lack of response to ambulatory treatment were related to unfavourable clinical progress.

Dental considerations and recommendations in Eisenmenger syndrome: A report of an unusual paediatric case.

BACKGROUND: Eisenmenger syndrome (ES) is a heart cyanotic condition characterised by elevated pulmonary vascular resistance and an intra-cardiac right-to-left shunting of blood through a systemic-to-pulmonary circulation connection. Affected children usually exhibit severe hypoxia, clubbing of fingers/toes, haemoptysis, anaemia, and organ damage. CASE REPORT: During autumn 2015, the patient and her parents arrived at the paediatric dentistry clinic. The patient presented with the main complaint of generalised inflamed gingival tissues, severely protruded upper incisors, and evident abnormal mouth breathing. TREATMENT: This was performed under local analgesia, rubber-dam isolation, and antimicrobial prophylaxis with amoxicillin (50 mg/kg). The patient's parents agreed to the treatment plan through a signed informed consent. This treatment consisted of the placement of pit and fissure sealants on the four permanent first molars (which included enamel preparation with fissurotomy burs), in-depth gingiva/dental frequent cleanings, local fluoride varnish applications, and an exhaustive programme of at-home oral hygiene (brushing, flossing, and chlorhexidine mouth rinses), including adequate nutrition. Gingivoplasty surgery to remove residual enlarged tissues was indicated for the near future. FOLLOW-UP: The child did not return to the clinic. When contacted, the parents reported that their daughter's systemic condition worsened significantly. She was confined to a bed at home under palliative care, with a life-span expectation of only a few months. CONCLUSION: Comprehensive dental care of children with ES requires careful consideration of their medical condition, and dental care delivery should be coordinated with the paediatric cardiologist. General analgesia should be considered only in strictly selected cases, due to the high peri-operative mortality reported.

Activation of aryl hydrocarbon receptor regulates the LPS/IFNγ-induced inflammatory response by inducing ubiquitin-proteosomal and lysosomal degradation of RelA/p65.

Several studies have identified the aryl hydrocarbon receptor (AhR) as a negative regulator of the innate and adaptive immune responses. However, the molecular mechanisms by which this transcription factor exerts such modulatory effects are not well understood. Interaction between AhR and RelA/p65 has previously been reported. RelA/p65 is the major NFκB subunit that plays a critical role in immune responses to infection. The aim of the present study was to determine whether the activation of AhR disrupted RelA/p65 signaling in mouse peritoneal macrophages by decreasing its half-life. The data demonstrate that the activation of AhR by TCDD and ß-naphthoflavone (ß-NF) decreased protein levels of the pro-inflammatory cytokines TNF-α, IL-6 and IL-12 after macrophage activation with LPS/IFNγ. In an AhR-dependent manner, TCDD treatment induces RelA/p65 ubiquitination and proteosomal degradation, an effect dependent on AhR transcriptional activity. Activation of AhR also induced lysosome-like membrane structure formation in mouse peritoneal macrophages and RelA/p65 lysosome-dependent degradation. In conclusion, these results demonstrate that AhR activation promotes RelA/p65 protein degradation through the ubiquitin proteasome system, as well as through the lysosomes, resulting in decreased pro-inflammatory cytokine levels in mouse peritoneal macrophages.

Fundamentals in Biostatistics for Research in Pediatric Dentistry: Part I - Basic Concepts.

The purpose of this report was to provide the reader with some basic concepts in order to better understand the significance and reliability of the results of any article on Pediatric Dentistry. Currently, Pediatric Dentists need the best evidence available in the literature on which to base their diagnoses and treatment decisions for the children's oral care. Basic understanding of Biostatistics plays an important role during the entire Evidence-Based Dentistry (EBD) process. This report describes Biostatistics fundamentals in order to introduce the basic concepts used in statistics, such as summary measures, estimation, hypothesis testing, effect size, level of significance, p value, confidence intervals, etc., which are available to Pediatric Dentists interested in reading or designing original clinical or epidemiological studies.

Conjugation of SUMO to p85 leads to a novel mechanism of PI3K regulation.

Class IA phosphatidylinositol 3-kinases (PI3Ks) are composed of p110 catalytic and p85 regulatory subunits. How regulatory subunits modulate PI3K activity remains only partially understood. Here we identified SUMO (small ubiquitin-related modifier) as a new player modulating this regulation. We demonstrate that both p85ß and p85α are conjugated to SUMO1 and SUMO2. We identified two lysine residues located at the inter-SH2 domain on p85ß, a critical region required for inhibition of p110, as being required for SUMO conjugation. A SUMOylation-defective mutant p85ß shows higher activation of the PI3K pathway, and increased cell migration and transformation. Moreover, the cancer-related KS459del mutant in p85α was less efficiently SUMOylated compared with the wild-type protein. Finally, our results show that SUMO modulates p85 tyrosine phosphorylation, a modification correlating with PI3K pathway activation. Thus, SUMO reduces the levels of tyrosine-phosphorylated-p85 while loss of SUMOylation results in increased tyrosine phosphorylation of p85. In summary, we identify SUMO as a new important player in the regulation of the PI3K pathway through modulation of p85.

Chitooligosaccharides as novel ingredients of fermented foods.

Chitooligosaccharides (COSs) have been clinically evaluated for their immunostimulating effects after oral intake. Similar to dietary supplements, prebiotics and biopreservatives, these water-soluble bioactives are easily incorporated into dairy products and beverages. Notwithstanding, the use of COS in fermented foods would be limited by its antimicrobial properties. In order to study the interaction with yoghurts as a model of fermented food, the effects of COS on chemical composition, viability, morphology and metabolism of lactic acid bacteria, fatty acid profiles and conjugated linoleic acid (CLA) were assessed over 28 days and after chemical digestion. There were no significant differences between the nutritional composition of controls and yoghurts supplemented with concentrations up to 0.1% w/w of COS. However, the acidification of milk decreased at 0.5% (p < 0.05) and the formation of yoghurt failed at 3.0%, without affecting viable counts. Lipid hydrolysis of yoghurts supplemented with 0.1% COS was not affected by chemical digestion. No significant differences were found between CLA percentages of controls and supplemented yoghurts after digestion. Although the nutritional composition, fatty acids and viable counts were not significantly modified after COS supplementation, the present study shows that COS diminishes bacterial acidification at concentrations higher than 0.1%, thus limiting the amounts that could be added to yoghurt.

Activation of AHR mediates the ubiquitination and proteasome degradation of c-Fos through the induction of Ubcm4 gene expression.

The ubiquitin-proteasome system (UPS) is a specific, non-lysosomal pathway responsible for the controlled degradation of abnormal and short-half-life proteins. Despite its relevance in cell homeostasis, information regarding control of the UPS component gene expression is lacking. Data from a recent study suggest that the aryl hydrocarbon receptor (AHR), a ligand-dependent transcription factor, might control the expression of several genes encoding for UPS proteins. Here, we showed that activation of AHR by TCDD and ß-naphthoflavone (ß-NF) results in Ubcm4 gene induction accompanied by an increase in protein levels. UbcM4 is an ubiquitin-conjugating enzyme or E2 protein that in association with ubiquitin ligase enzymes or E3 ligases promotes the ubiquitination and 26S proteasome-mediated degradation of different proteins, including p53, c-Myc, and c-Fos. We also present data demonstrating increased c-Fos ubiquitination and proteasomal degradation through the AHR-mediated induction of UbcM4 expression. The present study shows that AHR modulates the degradation of proteins involved in cell cycle control, consistent with previous reports demonstrating an essential role of the AHR in cell cycle regulation.

Probiotics and their effect on oral bacteria count in children: a pilot study.

AIM: To assess the effect of the daily ingestion of a mixture of probiotics on the amount of Streptococcus mutans in the oral cavity of preschool-age patients with a high risk of caries. MATERIALS AND METHODS: Forty patients, aged between 4 and 6 years, with a high risk of dental caries were included in this pilot study. Patients were randomly assigned to two study groups: the Experimental Group (A) included patients who brushed their teeth and used fluoridated toothpaste in addition to consuming probiotics daily, and the Control Group (B) inclused patients who brushed their teeth and used fluoridated toothpaste but did not consume probiotics. Using the CariScreen, the microorganism count was determined at different times: baseline, 7, 14, 21 and 30 days. To identify the differences between both groups, a Mann-Whitney U test was performed, with a significance level of 0.05. RESULTS: It was observed that both groups showed similar microbial counts at the beginning of the trial (p>0.05), and a significant decrease in the count at the end of the study was found in the experimental group (p<0.05) 15 days after suspending ingestion. CONCLUSION: We found a significant reduction of RLU values in preschool children who ingested the tested probiotics in relation to the baseline values and 15 days after ceasing consumption.

SUMOylation regulates AKT1 activity.

Serine threonine kinase AKT has a central role in the cell, controlling survival, proliferation, metabolism and angiogenesis. Deregulation of its activity underlies a wide range of pathological situations, including cancer. Here we show that AKT is post-translationally modified by the small ubiquitin-like modifier (SUMO) protein. Interestingly, neither SUMO conjugation nor activation of SUMOylated AKT is regulated by the classical AKT targeting to the cell membrane or by the phosphoinositide 3-kinase pathway. We demonstrate that SUMO induces the activation of AKT, whereas, conversely, down-modulation of the SUMO machinery diminishes AKT activation and cell proliferation. Furthermore, an AKT SUMOylation mutant shows reduced activation, and decreased anti-apoptotic and pro-tumoral activities in comparison with the wild-type protein. These results identify SUMO as a novel key regulator of AKT phosphorylation and activity.

The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation.

Accurate regulation of nuclear factor-κB (NF-κB) activity is crucial to prevent a variety of disorders including immune and inflammatory diseases. Active NF-κB promotes IκBα and A20 expression, important negative regulatory molecules that control the NF-κB response. In this study, using two-hybrid screening we identify the RING-type zinc-finger protein 114 (RNF114) as an A20-interacting factor. RNF114 interacts with A20 in T cells and modulates A20 ubiquitylation. RNF114 acts as negative regulator of NF-κB-dependent transcription, not only by stabilizing the A20 protein but also IκBα. Importantly, we demonstrate that in T cells, the effect of RNF114 is linked to the modulation of T-cell activation and apoptosis but is independent of cell cycle regulation. Altogether, our data indicate that RNF114 is a new partner of A2O involved in the regulation of NF-κB activity that contributes to the control of signaling pathways modulating T cell-mediated immune response.

Kaposi's sarcoma-associated herpesvirus lana2 protein interacts with the pocket proteins and inhibits their sumoylation.

The pocket proteins retinoblastoma protein (pRb), p107 and p130 are the key targets of oncoproteins expressed by DNA tumor viruses. Some of these viral proteins contain an LXCXE motif that mediates the interaction with the three pocket proteins and the inhibition of the pRb SUMOylation. Kaposi's sarcoma herpesvirus (KSHV) contains at least two proteins that can regulate pRb function but, so far, a KSHV-encoded protein targeting p107 and p130 has not been identified. Here, we show that the KSHV latent protein LANA2 binds to pRb, p107 and p130. LANA2 contains an LXCXE motif that is required for bypassing pRb-mediated cell-cycle arrest and for inhibiting pRb SUMOylation. Finally, we demonstrate that, in addition to pRb, both p107 and p130 can be SUMOylated, and this modification is also inhibited by LANA2 in an LXCXE-dependent manner. These results demonstrate, for the first time, the SUMOylation of p107 or p130 and, so far, they represent the first example of a KSHV protein able to interact with the three pocket proteins and to inhibit their conjugation to SUMO.

Identification of the NF-κB inhibitor A20 as a key regulator for human adipogenesis.

The zinc-finger protein A20 is a key player in the negative feedback regulation of the nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) pathway in response to multiple stimuli. Tumor necrosis factor alpha (TNFα), a cytokine with pleiotropic effects on cellular proliferation and differentiation, dramatically increases A20 expression in all tissues. As TNFα inhibits adipocyte differentiation, we have determined the contribution of A20 to the adipogenic capacity of human mesenchymal stromal cells (MSCs). Here we show that A20 is constitutively expressed in MSCs, which previously has been observed only in cells that are either tumor or immune cells (T/B lymphocytes). TNFα stimulation induced a rapid degradation of A20 protein mediated exclusively by the proteasome in MSCs and not by caspases. This degradation is concomitant to the induction of its own mRNA, which suggests that a tight regulation of NF-κB signaling in MSCs is fundamental. On one hand, we demonstrate that the knockdown of A20-mediated transcript dramatically decreases the adipogenic capacity of MSCs, which correlates with the phenotype observed in the presence of TNFα. On the other hand, A20 overexpression blocks NF-κB activation and drives to increased adipogenesis, even in the presence of TNFα treatment. In conclusion, our data demonstrate that the presence of A20 allows MSCs to differentiate into adipocytes by maintaining NF-κB signaling at a basal state.

Evidence on antimicrobial properties and mode of action of a chitosan obtained from crustacean exoskeletons on Pseudomonas syringae pv. tomato DC3000.

Pseudomonas syringae pv. tomato DC3000 (Pto DC3000) causes bacterial speck of tomato, a widely spread disease that causes significant economical losses worldwide. It is representative of many bacterial plant diseases for which effective controls are still needed. Despite the antimicrobial properties of chitosan has been previously described in phytopathogenic fungi, its action on bacteria is still poorly explored. In this work, we report that the chitosan isolated from shrimp exoskeletons (70 kDa and 78 % deacetylation degree) exerts cell damage on Pto DC3000. Chitosan inhibited Pto DC3000 bacterial growth depending on its concentration, medium-pH, and presence of metal ion (Mg(+2)). Biochemical and cellular changes resulting in cell aggregation and impaired bacterial growth were also viewed. In vivo studies using fluorescent probes showed cell aggregation, increase in membrane permeability, and cell death, suggesting the chitosan antibacterial activity is due to its interaction as a polycation with Pto DC3000 membranes. Transmission electron microscopic analysis revealed that chitosan also caused morphological changes and damage in bacterial surfaces. Also, the disease incidence in tomato inoculated with Pto DC3000 was significantly reduced in chitosan pretreated seedlings, revealing a promising action of chitosan as nontoxic biopesticide in tomato plants. Indeed, a wider comprehensive knowledge of the mechanism of action of chitosan in phytopathogenic bacterial cells will increase the chances of its successful application to the control of spread disease in plants.

GSK3-SCF(FBXW7) targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase.

JunB, an activator protein-1 (AP-1) transcription factor component, acts either as a tumor suppressor or as an oncogene depending on the cell context. In particular, JunB is strongly upregulated in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) where it enhances cell proliferation. Although its overexpression is linked to lymphomagenesis, the mechanisms whereby JunB promotes neoplastic growth are still largely obscure. Here, we show that JunB undergoes coordinated phosphorylation-dependent ubiquitylation during the G2 phase of the cell cycle. We characterized a critical consensus phospho-degron that controls JunB turnover and identified GSK3 and SCF(FBXW7) as, respectively, the kinase and the E3 ubiquitin ligase responsible for its degradation in G2. Pharmacological or genetic inactivation of the GSK3-FBXW7-JunB axis induced accumulation of JunB in G2/M and entailed transcriptional repression of the DNA helicase DDX11, leading to premature sister chromatid separation. This abnormal phenotype due to dysregulation of the GSK3ß/JunB/DDX11 pathway is phenocopied in ALK-positive ALCL. Thus, our results reveal a novel mechanism by which mitosis progression and chromatid cohesion are regulated through GSK3/SCF(FBXW7)-mediated proteolysis of JunB, and suggest that JunB proteolysis in G2 is an essential step in maintaining genetic fidelity during mitosis.

Regulation of the tumor suppressor PTEN by SUMO.

The crucial function of the PTEN tumor suppressor in multiple cellular processes suggests that its activity must be tightly controlled. Both, membrane association and a variety of post-translational modifications, such as acetylation, phosphorylation, and mono- and polyubiquitination, have been reported to regulate PTEN activity. Here, we demonstrated that PTEN is also post-translationally modified by the small ubiquitin-like proteins, small ubiquitin-related modifier 1 (SUMO1) and SUMO2. We identified lysine residue 266 and the major monoubiquitination site 289, both located within the C2 domain required for PTEN membrane association, as SUMO acceptors in PTEN. We demonstrated the existence of a crosstalk between PTEN SUMOylation and ubiquitination, with PTEN-SUMO1 showing a reduced capacity to form covalent interactions with monoubiquitin and accumulation of PTEN-SUMO2 conjugates after inhibition of the proteasome. Moreover, we found that virus infection induces PTEN SUMOylation and favors PTEN localization at the cell membrane. Finally, we demonstrated that SUMOylation contributes to the control of virus infection by PTEN.

Leucemia mieloide aguda con t(8; 21)(q22; q22): reporte de casos / Acute myeloid leukaemia with t(8; 21)(q22; q22): case report

La leucemia mieloide aguda es una neoplasia hematopoyética caracterizada por la proliferación clonal de blastos inmaduros en médulas ósea interfiriendo con sus funciones normales. Tiene una supervivencia aproximada de 35% afectando principalmente a adultos mayores de 60 años y niños menores de un año y preferentemente al sexo masculino. Un hallazgo frecuente es la presencia de la translocación cromosómica t (8; 21) (q22; q22) que involucra a los genes RUNX1 y RUNX1T1. La detección de esta alteración tiene implicancia diagnóstica y pronóstica de la enfermedad. El objetivo de este trabajo es describir y reportar dos casos de leucemia mieloide aguda en pacientes masculinos de 14 y 24 años que presentaron clínica, laboratorio y morfología típicos de la enfermedad pero con edad de aparición no habitual, enfatizando además, el pronóstico bueno desde el punto de vista citogenético de esta translocación en ambos casos.

Acute myeloid leukemia is a haematopoietic neoplasia characterized by clonal proliferation of immature blasts in bone marrow, interfering with its normal functions. Overall survival is about 35% affecting mainly male adults over 60 years old and infants under one year old. Genetic translocation t(8;21)(q22;q22) is a recurrent finding and involves RUNX1 and RUNX1T1 genes. The detection of this genetic translocation is relevant to the diagnosis and prognosis of the disease. The objective of this work is to report two cases of acute myeloid leukaemia in 14 and 24 years old male patients with typical clinical, laboratorial and morphological findings but with unusual appearing ages, emphasizing the good prognosis from the genetic point of view of this translocation in both cases.

Intergeneric phylogenetic relationships in catfishes of the Loricariinae (Siluriformes: Loricariidae), with the description of Fonchiiloricaria nanodon: a new genus and species from Peru.

Recent investigations in the upper Río Huallaga in Peru revealed the presence of an intriguing species of the Loricariinae. To characterize and place this species within the evolutionary tree of the subfamily, a molecular phylogeny of this group was inferred based on the 12S and 16S mitochondrial genes and the nuclear gene F-reticulon4. The phylogeny indicated that this distinctive species was a member of the subtribe Loricariina. Given its phylogenetic placement, and its unusual morphology, this species is described as a new genus and new species of Loricariinae: Fonchiiloricaria nanodon. This new taxon is diagnosed by usually possessing one to three premaxillary teeth that are greatly reduced; lips with globular papillae on the surface; the distal margin of lower lip bearing short, triangular filaments; the premaxilla greatly reduced; the abdomen completely covered by plates, with the plates between lateral abdominal plates small and rhombic; a caudal fin with 14 rays; the orbital notch absent; five lateral series of plates; dorsal-fin spinelet absent; preanal plate present, large and solid, and of irregular, polygonal shape, the caudal peduncle becoming more compressed posteriorly for the last seven to 10 plates.

Sediment and pollutant load modelling using an integrated urban drainage modelling toolbox: an application of City Drain.

Numerical and computational modelling of flow and pollutant dynamics in urban drainage systems is becoming more and more integral to planning and design. The main aim of integrated flow and pollutant models is to quantify the efficiency of different measures at reducing the amount of pollutants discharged into receiving water bodies and minimise the consequent negative water quality impact. The open source toolbox CITY DRAIN developed in the Matlab/Simulink environment, which was designed for integrated modelling of urban drainage systems, is used in this work. The goal in this study was to implement and test computational routines for representing sediment and pollutant loads in order to evaluate catchment surface pollution. Tested models estimate the accumulation, erosion and transport of pollutants--aggregately--on urban surfaces and in sewers. The toolbox now includes mathematical formulations for accumulation of pollutants during dry weather period and their wash-off during rainfall events. The experimental data acquired in a previous research project carried out by the Environmental Engineering Research Centre (CIIA) at the Universidad de los Andes in Bogotá (Colombia) was used for the calibration of the models. Different numerical approaches were tested for their ability to calibrate to the sediment transport conditions. Initial results indicate, when there is more than one peak during the rainfall event duration, wash-off processes probably can be better represented using a model based on the flow instead of the rainfall intensity. Additionally, it was observed that using more detailed models (compared with an instantaneous approach) for representing pollutant accumulation do not necessarily lead to better results.