We evaluate the association between subtypes of early life stress (ELS; sexual abuse, physical abuse, emotional abuse, physical neglect, and emotional neglect) and psychiatric disorders in adults. The sample was composed of 81 adult psychiatric patients treated at the Day Hospital Unit in Brazil. The patients were assessed using the Mini International Neuropsychiatric Interview according to diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The presence of ELS was confirmed by the Childhood Trauma Questionnaire, which investigates abuse and neglect subtypes. The patients were also evaluated for the severity of psychiatric symptoms through self-report questionnaires. A total of 71.6% of the patients experienced some type of severe ELS compared with 28.4% of the patients without ELS. Of these, 55.5% reported having experienced emotional abuse; 48.1%, physical neglect; 45.7%, emotional neglect; 39.5%, physical abuse; and 27.2%, sexual abuse. Our data showed that, among the ELS subtypes, emotional abuse was positively associated with psychopathology in adults, particularly with mood disorders (p < 0.05). The patients with a history of emotional abuse had higher severity scores in all symptoms, such as depression, hopelessness, suicidal ideation, anxiety, and impulsivity. These data demonstrate the impact of ELS, especially in cases of emotional abuse, as a trigger for psychiatric disorders and indicate that the severity of ELS is associated with severity of psychiatric symptoms. Therefore, further studies are needed to assess the importance of emotional abuse as a risk factor of severe psychopathology in adults.
Several studies have shown that basic emotions are responsible for a significant enhancement of early visual processes and increased activation in visual processing brain regions. It may be possible that the cognitive uncertainty and repeated behavioral checking evident in Obsessive Compulsive Disorder (OCD) is due to the existence of abnormalities in basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional-laden stimuli. The objective of the present study was to test if patients with OCD show evidence of altered basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional stimuli. Fifteen patients with OCD and 12 healthy controls underwent functional magnetic resonance imaging acquisition while being exposed to emotional pictures, with different levels of arousal, intended to trigger the defensive and appetitive basic survival circuits. Overall, the present results seem to indicate dissociation in the activity of the defense and appetitive survival systems in OCD. Results suggest that the clinical group reacts to basic threat with a strong activation of the defensive system mobilizing widespread brain networks (i.e., frontal, temporal, occipital-parietal, and subcortical nucleus) and blocking the activation of the appetitive system when facing positive emotional triggers from the initial stages of visual processing (i.e., superior occipital gyrus).
Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccines stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus.
In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLe(x)) along with a concomitant decrease in ?2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, ?2?1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLe(x) and lower ?2,6-sialic acid content on the glycans of their ?2?1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLe(x) and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of ?2?1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion.
Evidence indicates that early life stress (ELS) can induce persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis to respond to stress in the adult life that leads to depression. These appear to be related to the impairment of HPA hormones through binding to glucocorticoid (GR) and mineralocorticoid receptors (MR). The aim of this study was to evaluate the impact of ELS in HPA axis response to challenges with GR and MR agonists in depressed patients.
The incidence of Inflammatory Bowel Disease (IBD) is increasing worldwide and the underlying molecular mechanisms are far from being fully elucidated. Herein, we evaluated the role of N-glycosylation dysregulation in T cells as a key mechanism in the Ulcerative Colitis (UC) pathogenesis.The evaluation of the branched N-glycosylation levels and profile of intestinal T Cell Receptor (TCR) were assessed in colonic biopsies from UC patients and healthy controls. Expression alterations of glycosyltransferase gene MGAT5 were also evaluated. We demonstrated that UC patients exhibit a dysregulation of TCR branched N-glycosylation on lamina propria T lymphocytes. Patients with severe UC showed the most pronounced defect on N-glycan branching in T cells. Moreover, UC patients showed a significant reduction of MGAT5 gene transcription in T lymphocytes. In this study we disclose for the first time that a deficiency in branched N-glycosylation on TCR due to a reduced MGAT5 gene expression is a new molecular mechanism underlying UC pathogenesis, being a potential novel biomarker with promising clinical and therapeutic applications.
Parkinsons disease (PD) is a progressive neurodegenerative disorder, primarily characterized by motor symptoms such as tremor, rigidity, bradykinesia, stiffness, slowness and impaired equilibrium. Although the motor symptoms have been the focus in PD, slight cognitive deficits are commonly found in non-demented and non-depressed PD patients, even in early stages of the disease, which have been linked to the subsequent development of pathological dementia. Thus, strongly reducing the quality of life (QoL). Both levodopa therapy and deep brain stimulation (DBS) have yield controversial results concerning the cognitive symptoms amelioration in PD patients. That does not seems to be the case with transcranial direct current stimulation (tDCS), although better stimulation parameters are needed. Therefore we hypothesize that simultaneously delivering cathodal tDCS (or ctDCS), over the right prefrontal cortex delivered with anodal tDCS (or atDCS) to left prefrontal cortex could be potentially beneficial for PD patients, either by mechanisms of homeostatic plasticity and by increases in the extracellular dopamine levels over the striatum.
Pharmacological treatment is considered indispensable to major depressive disorder. In spite of this, a significant number of patients do not respond adequately to treatment based only on medication, presenting high relapse and recurrence rates. Therefore, psychosocial interventions, such as psychoeducation, have been increasingly recognized as an essential component in the treatment of depression, associated with pharmacological strategies. Thus, the aim of the present systematic review was to evaluate the effectiveness of psychoeducation for patients with unipolar depression, analyzing the evidence from the literature.
Understanding the determinants of Helicobacter pylori infection in adults is essential to predict the burden of H. pylori-related diseases. We aimed to estimate the prevalence and incidence of H. pylori infection and to identify its major sociodemographic correlates in an urban population from the North of Portugal.
Gastric cancer has a high incidence and mortality, so there is a pressing need to understand the underlying molecular mechanisms in order to discover novel biomarkers. Glycosylation alterations are frequent during gastric carcinogenesis and cancer progression. This review describes the role of glycans from the initial steps of the carcinogenesis process, in which Helicobacter pylori adheres to host mucosa glycans and modulates the glycophenotype, as well as how glycans interfere with epithelial cell adhesion by modulating epithelial cadherin functionality in gastric cancer progression. Other mechanisms regulating gastric cancer malignant behavior are discussed, such as increased sialylation interfering with key signaling pathways and integrin glycosylation leading to an invasive phenotype. Applications of these glycosylation alterations in the clinical management of gastric cancer patients are discussed.
E-cadherin is a cell-cell adhesion molecule and the dysfunction of which is a common feature of more than 70% of all invasive carcinomas, including gastric cancer. Mechanisms behind the loss of E-cadherin function in gastric carcinomas include mutations and silencing at either the DNA or RNA level. Nevertheless, in a high percentage of gastric carcinoma cases displaying E-cadherin dysfunction, the mechanism responsible for E-cadherin dysregulation is unknown. We have previously demonstrated the existence of a bi-directional cross-talk between E-cadherin and two major N-glycan processing enzymes, N-acetylglucosaminyltransferase-III or -V (GnT-III or GnT-V).
Serious vaccine-associated adverse events are rare. To further minimize their occurrence and to provide adequate care to those affected, careful monitoring of immunization programs and case management is required. Unfounded vaccine safety concerns have the potential of seriously derailing effective immunization activities. To address these issues, vaccine pharmacovigilance systems have been developed in many industrialized countries. As new vaccine products become available to prevent new diseases in various parts of the world, the demand for effective pharmacovigilance systems in low- and middle-income countries (LMIC) is increasing. To help establish such systems in all countries, WHO developed the Global Vaccine Safety Blueprint in 2011. This strategic plan is based on an in-depth analysis of the vaccine safety landscape that involved many stakeholders. This analysis reviewed existing systems and international vaccine safety activities and assessed the financial resources required to operate them. The Blueprint sets three main strategic goals to optimize the safety of vaccines through effective use of pharmacovigilance principles and methods: to ensure minimal vaccine safety capacity in all countries; to provide enhanced capacity for specific circumstances; and to establish a global support network to assist national authorities with capacity building and crisis management. In early 2012, the Global Vaccine Safety Initiative (GVSI) was launched to bring together and explore synergies among on-going vaccine safety activities. The Global Vaccine Action Plan has identified the Blueprint as its vaccine safety strategy. There is an enormous opportunity to raise awareness for vaccine safety in LMIC and to garner support from a large number of stakeholders for the GVSI between now and 2020. Synergies and resource mobilization opportunities presented by the Decade of Vaccines can enhance monitoring and response to vaccine safety issues, thereby leading to more equitable delivery of vaccines worldwide.
The crystal structure of the title complex, [Cu(C5H7O2)I(C10H8N2)], in the space group P1 with Z = 4, is stabilized by ?-? interactions and weak C-H···I interactions. The presence of two molecules in the asymmetric unit is associated with different intermolecular ?-? interactions between two symmetry-related molecules of each type.
Links between carbohydrate metabolism and virulence in Streptococcus pneumoniae have been recurrently established. To investigate these links further we developed a chemically defined medium (CDM) and standardized growth conditions that allowed for high growth yields of the related pneumococcal strains D39 and R6. The utilization of the defined medium enabled the evaluation of different environmental and nutritional factors on growth and fermentation patterns under controlled conditions of pH, temperature and gas atmosphere. The same growth conditions impacted differently on the nonencapsulated R6, and its encapsulated progenitor D39. A semi-aerobic atmosphere and a raised concentration of uracil, a fundamental component of the D39 capsule, improved considerably D39 growth rate and biomass. In contrast, in strain R6, the growth rate was enhanced by strictly anaerobic conditions and uracil had no effect on biomass. In the presence of oxygen, the difference in the growth rates was mainly attributed to a lower activity of pyruvate oxidase in strain D39. Our data indicate an intricate connection between capsule production in strain D39 and uracil availability. In this study, we have also successfully applied the in vivo NMR technique to study sugar metabolism in S. pneumoniae R6. Glucose consumption, end-products formation and evolution of intracellular metabolite pools were monitored online by (13)C-NMR. Additionally, the pools of NTP and inorganic phosphate were followed by (31)P-NMR after a pulse of glucose. These results represent the first metabolic profiling data obtained non-invasively for S. pneumoniae, and pave the way to a better understanding of regulation of central metabolism.
The influence of natural dissolved organic matter (DOM) on acute waterborne Cu toxicity was evaluated in the euryhaline copepod Acartia tonsa at 3 different water salinities. Three sources of freshwater DOM (extracted by reverse osmosis) and 2 sources of marine DOM (extracted using a solid-phase technique) were used. Artificial salt water was used to prepare the experimental media. Different combinations of Cu concentrations and DOM sources and concentrations were tested at salinities of 5, 15, and 30 ppt. Toxicity data (48-h median lethal concentration [LC50] values) were calculated based on dissolved Cu concentrations. In a broad view, data showed that increasing salinity was protective against the acute waterborne Cu toxicity. In general, Cu toxicity was also lower in the presence than in the absence of DOM. Toxicity (48-h LC50) values from all treatments at the same salinity showed a positive linear relationship with the dissolved organic carbon (DOC). Thus, the protective effect of DOM against the acute Cu toxicity seems to be dependent mainly on the DOM concentration. However, it seems also to be dependent to some extent on the source of DOM used. In summary, findings reported in the present study clearly indicate that both salinity and DOM (source and concentration) should be taken into account in the development of an estuarine version of the biotic ligand model.
The aim of the present study was to investigate if disordered eating behaviors predicted the development of sleep disturbances. A total of 870 students participated at baseline, 592 one year later (T1) and 305 two years later (T2). The Eating Attitudes Test-40 was used to assess global disordered eating behaviors, dietary concerns (DC), bulimic behaviors (BB) and social pressure to eat (SPE). Sleep disturbances were assessed by two items related to difficulties initiating sleep (DIS) and maintaining sleep (DMS). A sleep disturbance index (SDI) was calculated by summing DIS and DMS scores. Results revealed that global disordered eating behaviors at baseline predicted DIS, DMS and SDI at T1 and T2. Students with increased BB and SPE scores at baseline were more likely to experience sleep onset and sleep maintenance difficulties in the long term. These results suggest that assessment and correction of eating behaviors might prevent sleep disturbances.
Changes in glycosylation are considered a hallmark of cancer, and one of the key targets of glycosylation modifications is E-cadherin. We and others have previously demonstrated that E-cadherin has a role in the regulation of bisecting GlcNAc N-glycans expression, remaining to be determined the E-cadherin-dependent signaling pathway involved in this N-glycans expression regulation. In this study, we analysed the impact of E-cadherin expression in the activation profile of receptor tyrosine kinases such as insulin receptor (IR) and IGF-I receptor (IGF-IR). We demonstrated that exogenous E-cadherin expression inhibits IR, IGF-IR and ERK 1/2 phosphorylation. Stimulation with insulin and IGF-I in MDA-MD-435 cancer cells overexpressing E-cadherin induces a decrease of bisecting GlcNAc N-glycans that was accompanied with alterations on E-cadherin cellular localization. Concomitantly, IR/IGF-IR signaling activation induced a mesenchymal-like phenotype of cancer cells together with an increased tumor cell invasion capability. Altogether, these results demonstrate an interplay between E-cadherin and IR/IGF-IR signaling as major networking players in the regulation of bisecting N-glycans expression, with important effects in the modulation of epithelial characteristics and tumor cell invasion. Here we provide new insights into the role that Insulin/IGF-I signaling play during cancer progression through glycosylation modifications.
Pyruvate oxidase is a key function in the metabolism and lifestyle of many lactic acid bacteria and its activity depends on the presence of environmental oxygen. In Streptococcus pneumoniae the protein has been suggested to play a major role in metabolism and has been implicated in virulence, oxidative stress survival and death in stationary phase. Under semi-aerobic conditions, transcriptomic and metabolite profiling analysis of a spxB mutant grown on glucose showed minor changes compared to the wild type, apart from the significant induction of two operons involved in carbohydrate uptake and processing. This induction leads to a change in the sugar utilization capabilities of the bacterium, as indicated by the analysis of the growth profiles of the D39 parent and spxB mutant on alternative carbohydrates. Metabolic analysis and growth experiments showed that inactivation of SpxB has no effect on the glucose fermentation pattern, except under aerobic conditions. More importantly, we show that mutation of spxB results in the production of increased amounts of capsule, the major virulence factor of S. pneumoniae. Part of this increase can be attributed to induction of capsule operon (cps) transcription. Therefore, we propose that S. pneumoniae utilizes pyruvate oxidase as an indirect sensor of the oxygenation of the environment, resulting in the adaption of its nutritional capability and the amount of capsule to survive in the host.
The enormous biologic complexity of human cancer has stimulated the development of more appropriate experimental models that could resemble in a natural and spontaneous manner the physiopathologic aspects of cancer biology. Companion animals have many desired characteristics that fill the gap between in vitro and in vivo studies, and these characteristics have proven to be important in understanding many complex molecular aspects of human cancer. Spontaneous tumors in dogs share a wide variety of epidemiologic, biologic, and clinical features with human cancer, which makes this animal model both attractive and underused in oncology research. In this review, we summarize the importance of naturally occurring canine tumors as valuable tools for studying numerous aspects of human cancer as well as the potential use of this animal model for the development of new cancer treatments. We address specifically the use of canine mammary tumors as an increasingly powerful model to study human breast cancer.
In gram-positive bacteria, the transcriptional regulator CcpA is at the core of catabolite control mechanisms. In the human pathogen Streptococcus pneumoniae, links between CcpA and virulence have been established, but its role as a master regulator in different nutritional environments remains to be elucidated. Thus, we performed whole-transcriptome and metabolic analyses of S. pneumoniae D39 and its isogenic ccpA mutant during growth on glucose or galactose, rapidly and slowly metabolized carbohydrates presumably encountered by the bacterium in different host niches. CcpA affected the expression of up to 19% of the genome covering multiple cellular processes, including virulence, regulatory networks and central metabolism. Its prevalent function as a repressor was observed on glucose, but unexpectedly also on galactose. Carbohydrate-dependent CcpA regulation was also observed, as for the tagatose 6-phosphate pathway genes, which were activated by galactose and repressed by glucose. Metabolite analyses revealed that two pathways for galactose catabolism are functionally active, despite repression of the Leloir genes by CcpA. Surprisingly, galactose-induced mixed-acid fermentation apparently required CcpA, since genes involved in this type of metabolism were mostly under CcpA-repression. These findings indicate that the role of CcpA extends beyond transcriptional regulation, which seemingly is overlaid by other regulatory mechanisms. In agreement, CcpA influenced the level of many intracellular metabolites potentially involved in metabolic regulation. Our data strengthen the view that a true understanding of cell physiology demands thorough analyses at different cellular levels. Moreover, integration of transcriptional and metabolic data uncovered a link between CcpA and the association of surface molecules (e.g. capsule) to the cell wall. Hence, CcpA may play a key role in mediating the interaction of S. pneumoniae with its host. Overall, our results support the hypothesis that S. pneumoniae optimizes basic metabolic processes, likely enhancing in vivo fitness, in a CcpA-mediated manner.
Some authors have speculated that the cognitive component (P3) of the Event-Related Potential (ERP) can function as a psychophysiological measure of sexual interest. The aim of this study was to determine if the P3 ERP component in a workload task can be used as a specific and objective measure of sexual motivation by comparing the neurophysiologic response to stimuli of motivational relevance with different levels of valence and arousal. A total of 30 healthy volunteers watched different films clips with erotic, horror, social-positive and social-negative content, while answering an auditory oddball paradigm. Erotic film clips resulted in larger interference when compared to both the social-positive and auditory alone conditions. Horror film clips resulted in the highest levels of interference with smaller P3 amplitudes than erotic and also than social-positive, social-negative and auditory alone condition. No gender differences were found. Both horror and erotic film clips significantly decreased heart rate (HR) when compared to both social-positive and social-negative films. The erotic film clips significantly increased the skin conductance level (SCL) compared to the social-negative films. The horror film clips significantly increased the SCL compared to both social-positive and social-negative films. Both the highly arousing erotic and non-erotic (horror) movies produced the largest decrease in the P3 amplitude, a decrease in the HR and an increase in the SCL. These data support the notion that this workload task is very sensitive to the attentional resources allocated to the film clip, although they do not act as a specific index of sexual interest. Therefore, the use of this methodology seems to be of questionable utility as a specific measure of sexual interest or as an objective measure of the severity of Hypoactive Sexual Desire Disorder.
In this study, we tested the effects of transcranial Direct Current Stimulation (tDCS) on two set shifting tasks. Set shifting ability is defined as the capacity to switch between mental sets or actions and requires the activation of a distributed neural network. Thirty healthy subjects (fifteen per site) received anodal, cathodal and sham stimulation of the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1). We measured set shifting in both cognitive and motor tasks. The results show that both anodal and cathodal single session tDCS can modulate cognitive and motor tasks. However, an interaction was found between task and type of stimulation as anodal tDCS of DLPFC and M1 was found to increase performance in the cognitive task, while cathodal tDCS of DLPFC and M1 had the opposite effect on the motor task. Additionally, tDCS effects seem to be most evident on the speed of changing sets, rather than on reducing the number of errors or increasing the efficacy of irrelevant set filtering.
In this study, transparent conducting nanocrystalline ZnO:Ga (GZO) films were deposited by dc magnetron sputtering at room temperature on polymers (and glass for comparison). Electrical resistivities of 8.8 × 10-4 and 2.2 × 10-3 ? cm were obtained for films deposited on glass and polymers, respectively. The crack onset strain (COS) and the cohesive strength of the coatings were investigated by means of tensile testing. The COS is similar for different GZO coatings and occurs for nominal strains approx. 1%. The cohesive strength of coatings, which was evaluated from the initial part of the crack density evolution, was found to be between 1.3 and 1.4 GPa. For these calculations, a Youngs modulus of 112 GPa was used, evaluated by nanoindentation.
Obsessive Compulsive Disorder (OCD) involves failures in two main inhibitory processes, namely cognitive (obsessions) and behavioral (compulsions). Recent research has supported two cortical-subcortical pathways on OCD pathogenesis: (a) the frontostriatal loop (dorsolateral-caudate-striatum-thalamus) responsible for impairments of behavioral inhibition; (b) the orbitofrontal loop (orbitofrontal, medial prefrontal and cingulate) responsible for impairments with cognitive inhibitory processes. These failures in both cognitive and motor inhibitory systems may mediate several neuropsychological deficits in these patients, namely memory, attention, planning and decision making. But are those deficits related to specific hemispheric effects, namely functional imbalance between hemispheres? In this article we hypothesize that: (1) OCD patients have an inter-hemispheric functional imbalance, probably due to inadequate filtering at the thalamic level; (2) the restoration of inter-hemispheric balance, will be correlative to symptomatic improvement.
Tryparedoxins (TXNs) are oxidoreductases unique to trypanosomatids (including Leishmania and Trypanosoma parasites) that transfer reducing equivalents from trypanothione, the major thiol in these organisms, to sulfur-dependent peroxidases and other dithiol proteins. The existence of a TXN within the mitochondrion of trypanosomatids, capable of driving crucial redox pathways, is considered a requisite for normal parasite metabolism. Here this concept is shown not to apply to Leishmania. First, removal of the Leishmania infantum mitochondrial TXN (LiTXN2) by gene-targeting, had no significant effect on parasite survival, even in the context of an animal infection. Second, evidence is presented that no other TXN is capable of replacing LiTXN2. In fact, although a candidate substitute for LiTXN2 (LiTXN3) was found in the genome of L. infantum, this was shown in biochemical assays to be poorly reduced by trypanothione and to be unable to reduce sulfur-containing peroxidases. Definitive conclusion that LiTXN3 cannot directly reduce proteins located within inner mitochondrial compartments was provided by analysis of its subcellular localization and membrane topology, which revealed that LiTXN3 is a tail-anchored (TA) mitochondrial outer membrane protein presenting, as characteristic of TA proteins, its N-terminal end (containing the redox-active domain) exposed to the cytosol. This manuscript further proposes the separation of trypanosomatid TXN sequences into two classes and this is supported by phylogenetic analysis: i) class I, encoding active TXNs, and ii) class II, coding for TA proteins unlikely to function as TXNs. Trypanosoma possess only two TXNs, one belonging to class I (which is cytosolic) and the other to class II. Thus, as demonstrated for Leishmania, the mitochondrial redox metabolism in Trypanosoma may also be independent of TXN activity. The major implication of these findings is that mitochondrial functions previously thought to depend on the provision of electrons by a TXN enzyme must proceed differently.
The main aims of this article are twofold. First, to assess perfectionism dimensions in obsessive-compulsive disorder and eating disorders in comparison with psychiatric control (depression/anxiety) and non-clinical control groups. Second, to examine if perfectionism is specifically related to these different clinical conditions.
The purpose of the present study was to investigate the factor structure of the Beck Depression Inventory-II (BDI-II) in pregnancy and postpartum. Women were asked to fill in the BDI-II in their last trimester of pregnancy and at 3 months after delivery. A total of 331 pregnant women, with a mean age of 29.7 years (SD=4.6), and 354 mothers, aged 30.6 years (SD=4.6 years), answered the BDI-II. The first group was mainly nulliparas (65.6%) and the second group was mostly primiparas (57.4%). Factor analyses with principal components solution and varimax rotation were performed. Based on the scree test of Cattell a 2-factor solution and a 3-factor solution were explored. The 2-factor solution was identical in pregnancy and postpartum. Items loading in the Cognitive-Affective factor and in the Somatic-Anxiety factor were almost the same, though the Cognitive-Affective factor explained more of the BDI-II total variance in pregnancy, whereas in postpartum both factors explained similar total variances. The 3-factor solution of the BDI-II in pregnancy and postpartum slightly diverged. Besides the Cognitive-Affective and the Somatic-Anxiety factors, a third factor, Fatigue, was obtained in pregnancy while Guilt was the third factor identified in postpartum. This study reveals that the BDI-II 3-factor solution might be more appropriate to assess depressive symptoms in pregnancy and postpartum.
Knowledge of the in vivo physiology and metabolism of Streptococcus pneumoniae is limited, even though pneumococci rely on efficient acquisition and metabolism of the host nutrients for growth and survival. Because the nutrient-limited, hypoxic host tissues favor mixed-acid fermentation, we studied the role of the pneumococcal pyruvate formate lyase (PFL), a key enzyme in mixed-acid fermentation, which is activated posttranslationally by PFL-activating enzyme (PFL-AE). Mutations were introduced to two putative pfl genes, SPD0235 and SPD0420, and two putative pflA genes, SPD0229 and SPD1774. End-product analysis showed that there was no formate, the main end product of the reaction catalyzed by PFL, produced by mutants defective in SPD0420 and SPD1774, indicating that SPD0420 codes for PFL and SPD1774 for putative PFL-AE. Expression of SPD0420 was elevated in galactose-containing medium in anaerobiosis compared to growth in glucose, and the mutation of SPD0420 resulted in the upregulation of fba and pyk, encoding, respectively, fructose 1,6-bisphosphate aldolase and pyruvate kinase, under the same conditions. In addition, an altered fatty acid composition was detected in SPD0420 and SPD1774 mutants. Mice infected intranasally with the SPD0420 and SPD1774 mutants survived significantly longer than the wild type-infected cohort, and bacteremia developed later in the mutant cohort than in the wild type-infected group. Furthermore, the numbers of CFU of the SPD0420 mutant were lower in the nasopharynx and the lungs after intranasal infection, and fewer numbers of mutant CFU than of wild-type CFU were recovered from blood specimens after intravenous infection. The results demonstrate that there is a direct link between pneumococcal fermentative metabolism and virulence.
The main purpose of the present research was to explore gender-related associations between sleep disturbance and perfectionism dimensions in a large sample of undergraduate students. Perfectionism dimensions have been assessed using the Portuguese version of the Multidimensional Perfectionism Scale (Hewitt and Flett, 1991 , J Pers Soc Psychol 60:456; Soares et al., 2003 , Rev Port Psicossom 5:46) and sleep disturbance with two items concerning difficulties initiating sleep and difficulties maintaining sleep. A total of 1163 undergraduate students of both genders between 17 and 25 years of age completed the scale. Results from correlational and categorial analyses indicated that socially prescribed perfectionism was the only dimension associated with sleep disturbance in undergraduate students of both genders. Males with the highest levels of socially prescribed perfectionism were approximately twice more likely to report sleep disturbances than those with less socially prescribed perfectionism. Similar results were found within the female sample. Implications for future research and clinical practice are discussed.
The study explored the awareness of the Haute Autorité de Santé (High Health Authority, HAS) guidelines for migraine management in children among a random sample of 100 general practitioners (GPs) dichotomised in an urban and a rural group. A questionnaire conducted by phone included questions on knowledge of pediatric migraine acute treatment and preventive therapy, referral to a child neurologist as well as GPs awareness of HAS recommendations in general. Although 45% of GPs argued they were prescribing ibuprofen as first-line abortive drug, only 3% were aware of the recommended dose. Only 48% of GPs were agreeing to initiate preventive therapy. Fifty percent of GPs stated that they knew HAS guidelines but only 24% stated that they had read them. The only significant difference between urban and rural GPs concerned the initiation of preventive therapy. Continuing educational programmes on the implementation of pediatric migraine guidelines is strongly needed.
Amastigotes, the mammalian stage of Leishmania, must acquire iron from molecules accessing the macrophage parasitophorous vacuole (PV) where they inhabit. These molecules likely include non-heme and heme-bound forms of iron. Here we demonstrate that, in addition to the previously documented use of ferrous iron, Leishmania amastigotes are also capable of exploiting iron from hemin and hemoglobin for nutritional purposes. Moreover, evidence is presented that a ligand at the surface of amastigotes binds hemin with high-affinity (Kd=0.044nM). This ligand may function in intracellular transport of heme while hemoglobin internalization occurs through a different molecule. The co-existence in Leishmania amastigotes of different processes to acquire iron could constitute an infective strategy, ensuring parasites a substantial advantage in situations of iron limitation.
Leishmania infantum cytosolic tryparedoxin (LiTXN1) can be regarded as a potential candidate for drug targeting. This redox active molecule, which belongs to the thioredoxin superfamily, is one constituent of the hydroperoxide elimination cascade in L. infantum and may also be involved in other cellular processes such as DNA synthesis or host-parasite interaction. In order to validate LiTXN1 as a drug target we have employed a gene replacement strategy. We observed that substitution of both chromosomal LiTXN1 alleles was only possible upon parasite complementation with an episomal copy of the gene. Furthermore, contrary to control parasites carrying the empty vector, both the insect and the mammalian stages of L. infantum retained the episomal copy of LiTXN1 in the absence of drug pressure. These results confirm the essentiality of LiTXN1 throughout the life cycle of the parasite, namely in the disease-causing amastigote stage. In addition, the data obtained showed that disruption of one allele of this gene leads only to a 25% reduction in the expression of LiTXN1. Even though this does not affect promastigote growth and susceptibility to hydrogen peroxide, ex vivo infection assays suggest that wild-type levels of LiTXN1 are required for optimal L. infantum virulence.
Task switching, defined as the ability to flexibly switch between tasks in the face of goal shifting, is a central mechanism in cognitive control. Task switching is thought to involve both prefrontal cortex (PFC) and parietal regions. Our previous work has shown that it is possible to modulate set shifting tasks using 1 mA tDCS on both the left dorsolateral prefrontal cortex and the left primary motor area. However, it remains unclear whether the effects of PFC tDCS on task switching are hemisphere-dependent.
Film clips are an important tool for evoking emotional responses in the laboratory. When compared with other emotionally potent visual stimuli (e.g., pictures), film clips seem to be more effective in eliciting emotions for longer periods of time at both the subjective and physiological levels. The main objective of the present study was to develop a new database of affective film clips without auditory content, based on a dimensional approach to emotional stimuli (valence, arousal and dominance). The study had three different phases: (1) the pre-selection and editing of 52 film clips (2) the self-report rating of these film clips by a sample of 113 participants and (3) psychophysiological assessment [skin conductance level (SCL) and the heart rate (HR)] on 32 volunteers. Film clips from different categories were selected to elicit emotional states from different quadrants of affective space. The results also showed that sustained exposure to the affective film clips resulted in a pattern of a SCL increase and HR deceleration in high arousal conditions (i.e., horror and erotic conditions). The resulting emotional movie database can reliably be used in research requiring the presentation of non-auditory film clips with different ratings of valence, arousal and dominance.
N-acetylglucosaminyltransferase-III (GnT-III) is a glycosyltransferase encoded by Mgat3 that catalyzes the addition of ?1,4-bisecting-N-acetylglucosamine on N-glycans. GnT-III has been pointed as a metastases suppressor having varying effects on cell adhesion and migration. We have previously described the existence of a functional feedback loop between E-cadherin expression and GnT-III-mediated glycosylation. The effects of GnT-III-mediated glycosylation on E-cadherin expression and cellular phenotype lead us to evaluate Mgat3 and GnT-III-glycosylation role during Epithelial-Mesenchymal-Transition (EMT) and the reverted process, Mesenchymal-Epithelial-Transition (MET).
The present study analyses the modulatory effects of affective pictures in the early posterior negativity (EPN), the late positive potential (LPP) and the human startle response on both the peripheral (eye blink EMG) and central neurophysiological levels (Probe P3), during passive affective pictures viewing. The affective pictures categories were balanced in terms of valence (pleasant; unpleasant) and arousal (high; low). The data shows that EPN may be sensitive to specific stimulus characteristics (affective relevant pictures versus neutral pictures) associated with early stages of attentional processing. In later stages, the heightened attentional resource allocation as well as the motivated significance of the affective stimuli was found to elicit enhanced amplitudes of slow wave processes thought to be related to enhanced encoding, namely LPP,. Although pleasant low arousing pictures were effective in engaging the resources involved in the slow wave processes, the highly arousing affective stimuli (pleasant and unpleasant) were found to produce the largest enhancement of the LPP, suggesting that high arousing stimuli may are associated with increased motivational significance. Additionally the response to high arousing stimuli may be suggestive of increased motivational attention, given the heightened attentional allocation, as expressed in the P3 probe, especially for the pleasant pictures. The hedonic valence may then serve as a mediator of the attentional inhibition to the affective priming, potentiating or inhibiting a shift towards defensive activation, as measured by the startle reflex.
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