Decreased oxytocin levels related to social cognition impairment in borderline personality disorder.

INTRODUCTION: Dysfunctions in the oxytocin system have been reported in patients with borderline personality disorder (BPD). Deficits could be related to interpersonal hypersensitivity, which has been previously associated with failures in social cognition (SC) in this disorder, especially in Theory of Mind (ToM) skills. The aim of this work is to study the links between the oxytocin system and SC impairments in patients with BPD. METHOD: Plasma oxytocin levels (OXT) and protein expression of oxytocin receptors in blood mononuclear cells (OXTR) were examined in 33 patients with a diagnosis of BPD (age: M 28.85, DT = 8.83). Social cognition was assessed using the Movie for the Assessment of Social Cognition (MASC). Statistical associations between biochemical factors and different response errors in MASC were analyzed through generalized linear regression controlling for relevant clinical factors. RESULTS: Generalized linear regression showed a significant relationship between lower OXTR and overmentalization in BPD patients (OR = 0.90). CONCLUSIONS: This work supports the relationship between alterations in the oxytocin system and ToM impairments observed in BPD patients, enhancing the search for endophenotypes related to the phenotypic features of the disorder to improve current clinical knowledge and address more specific therapeutic targets.

Social cognition deficits in borderline personality disorder: Clinical relevance.

Interpersonal difficulties in borderline personality disorder (BDP) have been suggested to be related to impairments in Social Cognition (SC), mainly due to deficits in Theory of Mind (ToM). However, literature is scarce and ambiguous. This work aims to study the SC impairments in BPD patients, by the specific assessment of ToM deficits, and to investigate the relationship between these SC impairments and clinical variables. 82 BPD patients with BPD and 47 control subjects were assessed with the Movie for the Assessment of Social Cognition (MASC). Clinical variables of severity, chronicity, functionality and anxious-depressive symptomatology were recorded. BPD patients had fewer correct mentalization responses and more overmentalization, undermentalization, and absence of mentalization errors than controls. Chronicity was negatively correlated with overmentalization and positively correlated with undermentalization and absence of mentalization errors. Functionality was indirectly correlated with absence of mentalization. These results confirm previous reports of alterations in SC in BPD patients. Furthermore, this study shows that SC impairments in patients with BPD are dependent on characteristics such as chronicity or degree of functionality. The different ToM profiles in patients with BPD indicate the necessity of developing variants of mentalization therapy depending on the deficits of each patient.

Altered emotional response pattern related to complex trauma in patients with borderline personality disorder.

INTRODUCTION: This work aims to demonstrate, through the International Affective Picture System (IAPS) responses, an altered emotional pattern in borderline personality disorder (BPD) patients and to find a specific emotional response pattern by understanding their relationship with traumatic experiences and attachment bonds towards their primary caregivers. METHOD: A total of 50 BPD patients and 39 control patients were evaluated using the IAPS, and its assessment was carried out through the Self-Assessment Manikin (SAM). Paternal and maternal attachment bonds as well as traumatic experiences in BPD patients were evaluated. Statistical associations were analysed in the different variables. RESULTS: Significant differences between BPD and control patients were found in all emotional response components for pleasant, unpleasant and neutral images (p < .01), with one exception, the arousal in pleasant images. Patients' experience of traumatic experiences was positively related to scores on the happiness component of pleasant imagery (p = .057) and on the arousal component of unpleasant imagery (p = .058). Poorer maternal bonding in BPD patients was significantly related to lower scores on happiness (p < .01) and dominance (p < .05) components of pleasant imagery and all emotional response components for unpleasant imagery (p < .01). CONCLUSIONS: The results of the study confirm an impaired emotional response pattern in patients with borderline personality disorder (BPD), showing an emotional response to pleasant images similar to that of depression, while the pattern found to unpleasant images could be related to the complex trauma observed in these patients, which includes PTSD experiences such as sexual abuse and attachment trauma experiences.

Transdiagnostic Study of Impulsivity and Self-Injurious Behaviour in Unstable and Impulsive Disorders.

High comorbidity between borderline personality disorder (BPD) and eating disorders (ED) shows the necessity of developing transdiagnostic models, where impulsivity could play a relevant role in the manifestations of self-injurious behaviour.

A binary interaction map between turnip mosaic virus and Arabidopsis thaliana proteomes.

Viruses are obligate intracellular parasites that have co-evolved with their hosts to establish an intricate network of protein-protein interactions. Here, we followed a high-throughput yeast two-hybrid screening to identify 378 novel protein-protein interactions between turnip mosaic virus (TuMV) and its natural host Arabidopsis thaliana. We identified the RNA-dependent RNA polymerase NIb as the viral protein with the largest number of contacts, including key salicylic acid-dependent transcription regulators. We verified a subset of 25 interactions in planta by bimolecular fluorescence complementation assays. We then constructed and analyzed a network comprising 399 TuMV-A. thaliana interactions together with intravirus and intrahost connections. In particular, we found that the host proteins targeted by TuMV are enriched in different aspects of plant responses to infections, are more connected and have an increased capacity to spread information throughout the cell proteome, display higher expression levels, and have been subject to stronger purifying selection than expected by chance. The proviral or antiviral role of ten host proteins was validated by characterizing the infection dynamics in the corresponding mutant plants, supporting a proviral role for the transcriptional regulator TGA1. Comparison with similar studies with animal viruses, highlights shared fundamental features in their mode of action.

Reduced glucocorticoid receptor expression in blood mononuclear cells of patients with borderline personality disorder.

Introduction: Abnormal cortisol suppression in borderline personality disorder has been consistently reported in previous studies, suggesting that a hypersensitivity response of the hypothalamic-pituitary-adrenal (HPA) axis might occur in these patients. In this study, the abnormalities of the cortisol response in borderline personality disorder (BPD) are investigated through the cellular expression of the glucocorticoid receptors (GR) in BPD patients and its relationship with traumatic experiences. Methodology: Sixty-nine male and female patients diagnosed with BPD and 62 healthy controls were studied. Peripheral blood mononuclear cells were obtained to investigate the expression of glucocorticoid receptors. Western blot was used to measure protein expression. Statistical correlations of GR expression with BPD clinical features and intensity of previous traumatic events were investigated. Results: A significant decrease in the nuclear expression of glucocorticoid receptors was found in BPD patients compared to healthy controls in a regression analysis controlling for the effect of medication. GR expression decrease correlated significantly with clinical levels of anxiety and depression, but not with previous traumatic experiences in patients. Conclusions: BPD patients had a lower nuclear expression of glucocorticoid receptors than healthy controls, when it was controlled for the effect of medication. The reduced GR expression in BPD patients was not associated with previous traumatic events and might be associated with other aspects of BPD, such as emotional instability; more studies with larger samples of patients are still needed to understand the relevance and the implications of these findings.

Defects in plant immunity modulate the rates and patterns of RNA virus evolution.

It is assumed that host genetic variability for susceptibility to infection conditions virus evolution. Differences in host susceptibility can drive a virus to diversify into strains that track different defense alleles (e.g. antigenic diversity) or to infect only the most susceptible genotypes. Here, we have studied how variability in host defenses determines the evolutionary fate of a plant RNA virus. We performed evolution experiments with Turnip mosaic potyvirus in Arabidopsis thaliana mutants that had disruptions in infection-response signaling pathways or in genes whose products are essential for potyvirus infection. Plant genotypes were classified into five phenogroups according to their response to infection. We found that evolution proceeded faster in more restrictive hosts than in more permissive ones. Most of the phenotypic differences shown by the ancestral virus across host genotypes were removed after evolution, suggesting the combined action of selection and chance. When all evolved viral lineages were tested in all plant genotypes used in the experiments, we found compelling evidences that the most restrictive plant genotypes selected for more generalist viruses, while more permissive genotypes selected for more specialist viruses. Sequencing the genomes of the evolved viral lineages, we found that selection targeted the multifunctional genome-linked protein VPg in most host genotypes. Overall, this work illustrates how different host defenses modulate the rates and extent of virus evolution.

Dysfunction of Inflammatory Pathways and Their Relationship With Psychological Factors in Adult Female Patients With Eating Disorders.

The attempts to clarify the origin of eating disorders (ED) have not been completely successful and their etiopathogenesis remains unknown. Current research shows an activation of the immune response in neuropsychiatric diseases, including ED. We aimed to investigate immune response parameters in patients with ED and to identify psychological factors influencing the inflammatory response. The relationship between inflammation markers and impulsivity and affective symptomatology was explored as well. Thirty-four adult female patients with current diagnosis of ED, none of them under psychopharmacological treatment (excluding benzodiazepines), were included in this study. Patients were compared with a healthy control group of fifteen adult females. The levels of inflammatory markers and indicators of oxidative/nitrosative stress were evaluated in plasma and/or in peripheral blood mononuclear cells (PBMCs). Subjects were assessed by means of different ED evaluation tools. Additionally, the Barratt Impulsiveness Scale, the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were also employed. Patients with ED shown increased plasma levels of the pro-inflammatory nuclear factor kappa B (NFκB) and the cytokine tumor necrosis factor-alpha (TNF-α), among other factors and an increment in the oxidative/nitrosative stress as well as increased glucocorticoid receptor (GR) expression levels in their PBMCs. Moreover, the inflammatory prostaglandin E2 (PGE2) correlated with impulsiveness and the anti-inflammatory prostaglandin J2 (15d-PGJ2) correlated with depressive symptomatology. Our results point towards a relationship between the immune response and impulsiveness and between the immune response and depressive symptomatology in female adult patients with ED.

An algorithm combining procalcitonin and lung ultrasound improves the diagnosis of bacterial pneumonia in critically ill children: The PROLUSP study, a randomized clinical trial.

BACKGROUND: Lung ultrasound (LUS) and procalcitonin (PCT) are independently used to improve accuracy when diagnosing lung infections. The aim of the study was to evaluate the accuracy of a new algorithm combining LUS and PCT for the diagnosis of bacterial pneumonia. METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children <18 years old with suspected pneumonia admitted to pediatric intensive care unit were included, and randomized into experimental group (EG) or control group (CG) if LUS or chest X-Ray (CXR) were done as the first pulmonary image, respectively. PCT was determined. In patients with bacterial pneumonia, sensitivity, specificity, and predictive values of LUS, CXR, and of both combined with PCT were analyzed and compared. Concordance between the final diagnosis and the diagnosis concluded through the imaging test was assessed. RESULTS: A total of 194 children, with a median age of 134 (interquartile range [IQR]: 39-554) days, were enrolled, 96 randomized into the EG and 98 into the CG. Bacterial pneumonia was diagnosed in 97 patients. Sensitivity and specificity for bacterial pneumonia diagnosis were 78% (95% confidence interval [CI]: 70-85) and 98% (95% CI: 93-99) for LUS, 85% (95% CI: 78-90) and 53% (95% CI: 43-62) for CXR, 90% (95% CI: 83-94) and 85% (95% CI: 76-91) when combining LUS and PCT, and 95% (95% CI: 90-98) and 41% (95% CI: 31-52) when combining CXR and PCT. The positive predictive value for LUS and PCT was 88% (95% C:I 79%-93%) versus 68% (95% CI: 60-75) for CXR and PCT. The concordance between the final diagnosis and LUS had a kappa value of 0.69 (95% CI: 0.62-0.75) versus 0.34 (95% CI: 0.21-0.45) for CXR, (p < 0.001). CONCLUSIONS: The combination of LUS and PCT presented a better accuracy for bacterial pneumonia diagnosis than combining CXR and PCT. Therefore, its implementation could be a reliable tool for pneumonia diagnosis in critically ill children.

Inflammatory dysregulation in women with an eating disorder: Relationships with altered emotional reactivity.

BACKGROUND: Some studies suggest that inflammatory signaling dysregulation may contribute to eating disorder (ED) pathophysiology. However, little is known about the influence of inflammatory response on altered processes seen among patients with ED, such as emotional processing and reactivity. OBJECTIVES: The objectives were: (a) to investigate the systemic inflammatory response in ED women; and (b) to analyze the role of inflammatory markers in emotional reactivity. METHOD: Concentrations of several intercellular and intracellular inflammatory mediators (cytokines, prostaglandin by-products and enzymes, TBARS, and MAPK proteins) were quantified in plasma and PBMCs from 68 women with an ED (m = 22.01 years, SD = 9.15) and 35 healthy controls (m = 18.54 years, SD = 4.21). Moreover, emotional reactivity to affective pictures (those without either food or thinness content) was studied using the adult (>18 years old) sample (n = 41). RESULTS: Between-group differences were revealed for most markers (TNF-α, PGE2 , COX2, and ratio of activated MAPK proteins), pointing to increased inflammatory response in patients (p < .01). Women with ED showed heightened emotional reactivity, regardless of picture valence. Principal components derived from inflammatory markers showed an explanatory loading on patient's emotional reaction, in terms of valence and arousal. CONCLUSION: This study corroborates the altered systemic inflammatory response in patients with ED. The inflammatory dysregulation may contribute to ED phenotype, as seen by its relationship with heightened emotional reactivity, even though the inflammatory markers were not evaluated throughout the emotional reactivity protocol.

Executive Dysfunction Associated With the Primary Psychopathic Features of Borderline Personality Disorder.

Purpose: The aim of the present study is to investigate whether the presence of psychopathic features in BPD is related to dysfunction in executive functions and other neuropsychological functions in these patients. Methods: 82 patients diagnosed with borderline personality disorder and 54 control subjects were studied through clinical and neuropsychological evaluation protocols and the Levenson Psychopathy Inventory. Results: BPD patients showed significantly higher scores on both primary (F1) and secondary (F2) global rates of psychopathy, than controls. The results for these patients also showed a statistically significant association between high scores in primary psychopathy and deficits in executive functions. However, no associations were found between the scores of secondary psychopathy and executive dysfunction. Conclusion: Primary psychopathic features present in patients with BPD are associated with patterns of executive dysfunction. It would therefore be interesting to investigate the role of cognitive rehabilitation in the empathy dysfunctions within these disorders.

Inflammatory and antioxidant pathway dysfunction in borderline personality disorder.

INTRODUCTION: This study investigates the alteration of the inflammatory/oxidative pathway in patients with borderline personality disorder (BPD) and its relationship with clinical features of the disorder. METHODS: 49 BPD patients and 33 healthy control subjects were studied. Plasma levels of TBARS, nitrites, and the antioxidant enzymes CAT, GPx and SOD were measured. In addition, peripheral blood mononuclear cells were obtained to investigate levels of intracellular components of the inflammatory/oxidative pathway including the IκBα, NFκB, iNOS, COX2, Keap1, NQO1, and HO1. Western Blot and ELISA were used to measure protein expression. Patients were assessed for different clinical dimensions of BPD with scales for depression, anxiety, impulsivity and functioning. RESULTS: A significant decrease of IκBα levels and a significant increase of inflammatory factors, including NFκB, COX2 and iNOS levels were found in patients. On the other hand, a significant decrease was observed for all antioxidant enzymes in patients with BPD, except for HO1. The inflammatory factor NFκB showed a significant positive correlation with impulsivity scores. CONCLUSIONS: Patients with BPD presented an increased activation of several components of the inflammatory pathways, as well as an inhibition of the antioxidant path. These alterations appear partially correlated with the impulsivity scores in these patients.

Dysfunction of inflammatory pathways in adolescent female patients with anorexia nervosa.

BACKGROUND: The pathogenesis of Eating Disorders is still unknown. However, a growing body of evidence shows that there are changes in cytokine levels and an alteration in the stress response in patients with anorexia nervosa (AN). For this reason, we decided to test whether there are differences in immune parameters involved in the regulation of the inflammatory response between female adolescents with AN and healthy adolescents. METHODS: The sample 27 drug-naïve AN patients the study sample included 27 AN patients at a very early stage of the disease and 23 healthy controls. Plasma and peripheral blood mononuclear cells (PBMCs) were obtained for biochemical study. RESULTS: Plasma levels of the pro-inflammatory cytokines TNF-α and IL-1ß were significantly increased in patients with AN, while the levels of prostaglandins PGE2 (proinflammatory) and 15d-PGJ2, (anti-inflammatory) were lower compared with controls. Protein expression in PBMCs of cyclooxygenase-2 (COX-2) and the activated forms of the mitogen-activated protein kinases p38 and ERK were also increased in the AN group. Expression levels of the anti-inflammatory factor peroxisome proliferator-activated receptor gamma (PPARγ) were significantly decreased in patients. Plasma levels of lipid peroxidation markers -TBARS- were not increased in patients with AN. Components of the biochemical inflammatory response (COX-2, PGE2, TBARS, 15d-PGJ2, ERK, p65 NFκB) and glucocorticoid receptor -GR- expression and the scores on the impulsivity measures in the BARRATT, EDI and BITE questionnaires showed a significant correlation within the AN patients group. CONCLUSIONS: The results for female adolescent patients with AN indicate that there is a dysfunction of intra- and intercellular inflammatory pathways characterized by higher levels of pro-inflammatory parameters in plasma and a decrease in one of the controlling cytoplasmic-nuclear pathways implicated in their modulation (i.e. PPARγ) with, at this very early stage of the disease, no effect on oxidative stress markers plasma levels. Most notably, higher severity of illness (restrictive and purging behaviour) correlated with higher levels of inflammatory markers.

Impact of PLA/Mg films degradation on surface physical properties and biofilm survival.

New biocompatible and bioabsorbable materials are currently being developed for bone regeneration. These serve as scaffolding for controlled drug release and prevent bacterial infections. Films of polylactic acid (PLA) polymers that are Mg-reinforced have demonstrated they have suitable properties and bioactive behavior for promoting the osseointegration process. However little attention has been paid to studying whether the degradation process can alter the adhesive physical properties of the biodegradable film and whether this can modify the biofilm formation capacity of pathogens. Moreover, considering that the concentration of Mg and other corrosion products may not be constant during the degradation process, the question that arises is whether these changes can have negative consequences in terms of the bacterial colonization of surfaces. Bacteria are able to react differently to the same compound, depending on its concentration in the medium and can even become stronger when threatened. In this context, physical surface parameters such as hydrophobicity, surface tension and zeta potential of PLA films reinforced with 10% Mg have been determined before and after degradation, as well as the biofilm formation capacity of Staphylococcus epidermidis. The addition of Mg to the films makes them less hydrophobic and the degradation also reduces the hydrophobicity and increases the negative charge of the surface, especially over long periods of time. Early biofilm formation at 8 h is consistent with the physical properties of the films, where we can observe a reduction in the bacterial biofilm formation. However, after 24 h of incubation, the biofilm formation increases significantly on the PLA/Mg films with respect to PLA control. The explosive release of Mg ions and other corrosion products within the first hours were not enough to prevent a greater biofilm formation after this initial time. Consequently, the Mg addition to the polymer matrix had a bacteriostatic effect but not a bactericidal one. Future works should aim to optimize the design and biofunctionality of these promising bioabsorbable composites for a degradation period suitable for the intended application.

Intussusceptive Lymphangiogenesis in Lymphatic Malformations/Lymphangiomas.

Intussusception in lymphatic vessels has received less attention than in blood vessels. In tumors and pseudotumors of blood vessels with intravascular papillary structures, including sinusoidal hemangioma and intravascular papillary endothelial hyperplasia, we observed exuberant intussusceptive angiogenesis, as well as the similarity between papillae (term used by pathologists) and pillars/folds (hallmarks of intussusceptive angiogenesis). A similar response could be expected in lymphangiomas (lymphatic malformations and reactive processes rather than tumors) with papillae. The aim of this work is to assess whether papillae/pillars/folds and associated structures (vessel loops and septa) are present in lymphangiomas, and to establish the characteristics and formation of these structures. For this purpose, we selected lymphangiomas with intraluminal papillae (n = 18), including cystic, cavernous, circumscriptum, and progressive types, of which two cases of each type with a greater number of papillae were used for serial histologic sections and immunohistochemistry. The studies showed a) dilated lymphatic spaces giving rise to lymphatic-lymphatic vascular loops, which dissected and encircled perilymphatic structures (interstitial tissue structures/ITSs and pillars/posts), b) ITSs and pillars, surrounded by anti-podoplanin-positive endothelial cells, protruding into the lymphatic spaces (papillary aspect), and c) splitting, remodeling, linear arrangement, and fusion of papillae/pillars/folds, forming papillary networks and septa. In conclusion, as occurs in blood vessel diseases, the development of lymphatic vessel loops, papillae/pillars/folds, and septa (segmentation) supports intussusceptive lymphangiogenesis and suggests a piecemeal form of intussusception. This intussusceptive lymphangiogenesis in lymphatic diseases can provide a basis for further studies of lymphatic intussusception in other conditions, with clinical and therapeutic implications. Anat Rec, 302:2003-2013, 2019. © 2019 American Association for Anatomy.

Neuropsychological findings in recent onset schizophrenia and borderline personality disorder: a comparison study.

INTRODUCTION: Neurocognitive impairment is considered an essential symptom of schizophrenia, particularly in its early stages. Nonetheless, the neuropsychological features of borderline personality disorder (BPD) could cast doubt on the specificity of neurocognitive dysfunctions. The aim of this study is to determine whether neurocognitive deficits are specific to schizophrenia-spectrum conditions as compared to a similarly severe psychiatric illness like BPD. METHOD: A battery of neuropsychological tests was used to assess the abilities for attention, verbal memory and executive functions in a group of 34 borderline personality disorder (BPD) patients, 24 patients with first episode of a schizophrenia-spectrum disorder (FEP) and a group of 19 controls. RESULTS: ANOVA for multiple measures with subsequent post-hoc tests demonstrated significant effect sizes between controls and patients for all cognitive domains. However, the effect sizes of comparisons between both groups of patients were not significant. CONCLUSIONS: Results show significant neuropsychological impairment in both disorders when compared with normal controls, but no specific pattern of neurocognitive deficits for schizophrenia-spectrum disorders was found.

Response inhibition in borderline personality disorder: Neural and behavioral correlates.

Although response inhibition is thought to be important in borderline personality disorder (BPD), little is known about its neurophysiological basis. This study aimed to provide insight into this issue by capitalizaing on the high temporal resolution of electroencephalography and information provided by source localization methods. To this end, twenty unmedicated patients with BPD and 20 healthy control subjects performed a modified go/no-go task designed to better isolate the brain activity specifically associated with response inhibition. Event-related potentials (ERP) were measured and further analyzed at the scalp and source levels. Patients with BPD made more commission errors (failed inhibitions) than control subjects. Scalp ERP data showed that both groups displayed greater frontocentral P3 amplitude for no-go (response inhbition) than for go trials (response execution). However, source reconstruction data revealed that patients with BPD activated posterior parietal regions (precuneus) to inhibit their responses, whereas controls activated prefrontal regions (presupplementary motor area, preSMA). This dissociation was supported by a significant Region (precuneus, preSMA) x Trial Type (no-go, go) x Group (BPD, control) interaction. These findings extend our understanding of the neurophysiological basis of abnormal response inhibition in BPD, suggesting that patients with BPD recruit different brain regions for inhibiting prepotent responses compared to controls. Future research in larger, medication-naïve samples of patients with BPD is required to confirm and extend these findings.

Exploring the role of cellular homologous of the 30K-superfamily of plant virus movement proteins.

Genes orthologous to the 30K-superfamily of movement proteins (MP) from plant viruses have been recently discovered by bioinformatics analyses as integrated elements in the genome of most vascular plants. However, their functional relevance for plants is still unclear. Here, we undertake some preliminary steps into the functional characterization of one of these putative MP genes found in Arabidopsis thaliana. We found that the AtMP gene is expressed at different stages of the plant development, with accumulation being highest in flowers but lowest in mature siliques. We also found down-regulation of the gene may result in a small delay in plant development and in an exacerbation of the negative effect of salinity in germination efficiency. We have also explored whether changes in expression of the endogenous AtMP have any effect on susceptibility to infection with several viruses, and found that the infectivity of tobacco rattle tobravirus was strongly dependent on the expression of the endogenous AtMP. Finally, we have cloned the endogenous MP from four different plant species into an expression vector that allows for specifically assessing their activity as cell-to-cell movement proteins and have shown that though some may still retain the ancestral activity, they do so in a quite inefficient manner, thus suggesting they have acquired a novel function during adaptation to the host genome.

Going, going, gone: predicting the fate of genomic insertions in plant RNA viruses.

Horizontal gene transfer is common among viruses, while they also have highly compact genomes and tend to lose artificial genomic insertions rapidly. Understanding the stability of genomic insertions in viral genomes is therefore relevant for explaining and predicting their evolutionary patterns. Here, we revisit a large body of experimental research on a plant RNA virus, tobacco etch potyvirus (TEV), to identify the patterns underlying the stability of a range of homologous and heterologous insertions in the viral genome. We obtained a wide range of estimates for the recombination rate-the rate at which deletions removing the insertion occur-and these appeared to be independent of the type of insertion and its location. Of the factors we considered, recombination rate was the best predictor of insertion stability, although we could not identify the specific sequence characteristics that would help predict insertion instability. We also considered experimentally the possibility that functional insertions lead to higher mutational robustness through increased redundancy. However, our observations suggest that both functional and non-functional increases in genome size decreased the mutational robustness. Our results therefore demonstrate the importance of recombination rates for predicting the long-term stability and evolution of viral RNA genomes and suggest that there are unexpected drawbacks to increases in genome size for mutational robustness.

l-Carnitine ameliorates the oxidative stress response to angiotensin II by modulating NADPH oxidase through a reduction in protein kinase c activity and NF-κB translocation to the nucleus.

l-Carnitine (LC) exerts beneficial effects in arterial hypertension due, in part, to its antioxidant capacity. We investigated the signalling pathways involved in the effect of LC on angiotensin II (Ang II)-induced NADPH oxidase activation in NRK-52E cells. Ang II increased the generation of superoxide anion from NADPH oxidase, as well as the amount of hydrogen peroxide and nitrotyrosine. Co-incubation with LC managed to prevent these alterations and also reverted the changes in NADPH oxidase expression triggered by Ang II. Cell signalling studies evidenced that LC did not modify Ang II-induced phosphorylation of Akt, p38 MAPK or ERK1/2. On the other hand, a significant decrease in PKC activity, and inhibition of nuclear factor kappa B (NF-kB) translocation, were attributable to LC incubation. In conclusion, LC counteracts the pro-oxidative response to Ang II by modulating NADPH oxidase enzyme via reducing the activity of PKC and the translocation of NF-kB to the nucleus.