The role of the ferric uptake regulator (Fur) in regulation of Helicobacter pylori iron uptake

Background. Availability of the essential nutrient iron is thought to vary greatly in the gastric mucosa, and thus the human gastric pathogen Helicobacter pylori requires regulatory responses to these environmental changes. Bacterial iron-responsive regulation is often mediated by Ferric Uptake Regulator (Fur) homologs, and in this study we have determined the role of H. pylori Fur in regulation of H. pylori iron uptake. Methods. Wild-type H. pylori and fur mutant derivatives were compared after growth in ironrestricted and iron-replete conditions. Iron-uptake was measured using 55Fe-labeled iron, whereas gene expression was mon

Transdiagnostic psychiatry: Symptom profiles and their direct and indirect relationship with well-being

BACKGROUND: Heterogeneity and comorbidity in psychiatric disorders are common, however, little is known about the impact on well-being and the role of functional limitations. We aimed to identify transdiagnostic psychiatric symptom profiles and to study their association with well-being and the mediating role of functional limitations in a naturalistic psychiatric patient group. METHODS: We used four disorder-specific questionnaires to assess symptom severity within a sample of 448 psychiatric patients with stress-related and/or neurodevelopmental disorders and 101 healthy controls. Using both exploratory and confirmatory factor analyses we identified transdiagnostic symptom profiles, which we entered into a linear regression analysis to assess their association with well-being and the mediating role of functional limitations in this association. RESULTS: We identified eight transdiagnostic symptom profiles, covering mood, self-image, anxiety, agitation, empathy, non-social interest, hyperactivity and cognitive focus. Mood and self-image showed the strongest association with well-being in both patients and controls, while self-image also showed the highest transdiagnostic value. Functional limitations were significantly associated with well-being and fully mediated the relationship between cognitive focus and well-being. LIMITATIONS: The participant sample consisted of a naturalistic group of out-patients. While this strengthens the ecological validity and transdiagnostic perspective of this study, the patients with a single neurodevelopmental disorder were underrepresented. CONCLUSION: Transdiagnostic symptom profiles are valuable in understanding what reduces well-being in psychiatric populations, thereby opening new avenues for functionally meaningful interventions

Striatal connectopic maps link to functional domains across psychiatric disorders

Transdiagnostic approaches to psychiatry have significant potential in overcoming the limitations of conventional diagnostic paradigms. However, while frameworks such as the Research Domain Criteria have garnered significant enthusiasm among researchers and clinicians from a theoretical angle, examples of how such an approach might translate in practice to understand the biological mechanisms underlying complex patterns of behaviors in realistic and heterogeneous populations have been sparse. In a richly phenotyped clinical sample (n = 186) specifically designed to capture the complex nature of heterogeneity and comorbidity within- and between stress- and neurodevelopmental disorders, we use exploratory factor analysis on a wide range of clinical questionnaires to identify four stable functional domains that transcend diagnosis and relate to negative valence, cognition, social functioning and inhibition/arousal before replicating them in an independent dataset (n = 188). We then use connectopic mapping to map inter-individual variation in fine-grained topographical organization of functional connectivity in the striatum-a central hub in motor, cognitive, affective and reward-related brain circuits-and use multivariate machine learning (canonical correlation analysis) to show that these individualized topographic representations predict transdiagnostic functional domains out of sample (r = 0.20, p = 0.026). We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry

Molecular characterization of the surface layer proteins from Clostridium difficile.

Many bacteria express a surface-exposed proteinaceous layer, termed the S-layer, which forms a regular two-dimensional array visible by electron microscopy. Clostridium difficile is unusual in expressing two S-layer proteins (SLPs), which are of varying size in a number of strains. In an approach combining molecular biology with mass spectrometric sequencing strategies, we have identified the structural gene (slpA) for the S-layer from three strains of C. difficile. Both proteins are derived from a common precursor, and processing involves the removal of a signal peptide and a second cleavage to release the two mature SLPs. To our knowledge, this is the first example in which two SLPs have been shown to derive from a single gene product through post-translational processing, rather than from the expression of separate genes. The higher molecular weight (MW) SLP is highly conserved among the three strains, whereas the lower MW SLP shows considerable sequence diversity, reflecting the results from Western blotting. The high-MW SLP shows weak homology to N-acetyl muramoyl-L-alanine amidase from Bacillus subtilis, and both the native SLP from C. difficile and a recombinant protein expressed in Escherichia coli were found to display amidase activity by zymography. The high-MW SLPs showed evidence of glycosylation, whereas the lower MW proteins did not. A family of genes with sequence homology to the amidase domain of the high-MW SLP was identified in the C. difficile strain 630 genome, some of which are located in the same region of the genome as slpA and were shown by reverse transcription-polymerase chain reaction (RT-PCR) analysis to be transcribed

Resposta eritropoética de ratos em diferentes graus de parasitemia por Trypanosoma evansi Erithropoietic response in Trypanosoma evansi infected rats with different parasitaemia intensity

O Trypanosoma evansi é um protozoário hemoflagelado que causa, em várias espécies, uma doença caracterizada por altos níveis de parasitemia, com rápido desenvolvimento de anemia. Este trabalho teve como objetivo investigar a relação entre o grau de parasitemia e a alteração na eritropoese de ratos (Rattus norvegicus) da linhagem Wistar infectados experimentalmente com T. evansi. Foram utilizados 42 ratos, dos quais 36 foram inoculados pela via intraperitoneal com 0,2ml de sangue, contendo 2,5 x 104 parasitas. Seis ratos não-inoculados foram utilizados como controles. Após inoculação, a parasitemia foi avaliada a cada 12h. Os grupos para análise foram estipulados de acordo com a média de tripanossomas em 10 campos homogêneos focados aleatoriamente, sendo: A, controle; B, animais que apresentaram um grau de parasitemia entre 1-10 tripanossomas/campo; C, ratos com 11-20 tripanossomas/campo; D, ratos com 21-30 tripanossomas/campo; E, ratos com 31-40 tripanossomas/campo; F, 41-50 tripanossomas/campo; e G, ratos com mais de 51 tripanossomas/campo. Quando os animais apresentaram o número de protozoários equivalente ao grupo, foram coletadas amostras de sangue para realização de hemograma e dosagem de ferro, e foi realizada citologia de medula óssea para avaliação da relação mielóide:eritróide. A análise estatística mostrou redução significativa das hemácias e do hematócrito a partir de 31 tripanossomas/campo (grupos E, F e G; P<0,005) e a redução de hemoglobina ocorreu a partir de 41 tripanossomas/campo (grupos F e G; P<0,005). A relação mielóide:eritróide foi reduzida de 0,7 para 0,6 a partir de 41 tripanossomas/campo (grupos F e G; P<0,005). Não foram detectadas variações na concentração de ferro. Os dados obtidos demonstraram que ratos com parasitemia acima de 31 tripanossomas por campo desenvolvem uma anemia aguda, com um aumento compensatório na atividade hematopoética.<br>Trypanosoma evansi is a flagellate protozoan that causes a disease characterized by high parasitemia and acute anemia in various species. This study was aimed at evaluating and establishing a relationship between different parasitemia levels and eritropoyesis in Wistar rats (Rattus norvegicus) experimentally infected by T. evansi. Forty two animals were used. In 36 animals parasites were inoculated by intraperitoneal blood injection of 0.2ml containing 2.5x104 parasites. Six non-inoculated animals were used as controls. Parasitemia was evaluated every 12 hours and the animals were allocated in groups according to parasitemia levels. Then they were classified according to average number of parasites in 10 random homogeneous fields, Group A: control (not-inoculated); B: rats with 1-10 trypanosomes/field; C: 11-20 trypanosomes/field; D: 21-30 trypanosomes/field; E: 31-40 trypanosomes/field; F: 41-50 trypanosomes/field; G: more then 51. Blood samples were taken when the animals reached the correspondent group number of parasites. Hemogram and iron levels were evaluated and a bone marrow cytology was performed to detect the myeloid:erythroid ratio. Statistical analysis showed a significant reduction on red blood cells count and hematocrit from group E on and also hemoglobin on groups F and G. The myeloid:erythroid ratio reduced from 0.7 to 0.6 on groups F and G (P<0.005). Iron levels alterations were not detected. These data showed that Wistar rats with parasitemia higher then 31 parasites per field have an acute anemia associated to a compensatory hematopoietic activity