Prevalence of blaSHV genes in clinical isolates of Klebsiella pneumoniae at Saint Camille medical Center in Ouagadougou. Isolation of blaSHV11-like gene

Five bacterial strains (4 Klebsiella pneumoniae and 1 Escherichia coli) representative of pathogenic species and resistant to β-lactam antibiotics are investigated to isolate the genes responsible of β--lactamase activity. The use of engineering techniques enables us to show the widespread of blaSHV genes particularly in clinical isolates of K. pneumoniae. Our results highlighted an atypical blaSHV-11 gene. Key words: β--Lactamases, Klebsiella pneuminiae, blaSHV gene, Saint Camille medical centre, Ouagadougou. African Journal of Biotechnology Vol.3(9) 2004: 477-48

001 Predictive Value of Post Treatment Platelet Reactivity for Occurrence of Post-discharge Bleeding After Non ST Elevation Acute Coronary Syndrome

AimsWe assessed prospectively the association between occurrence of post-discharge non–CABG-related TIMI major and minor bleedings and post treatment platelet reactivity in patients with Non ST Elevation Acute Coronary Syndrome (NSTE ACS).Methods and Results597 consecutive patients admitted with NSTE ACS were prospectively included. Between hospital discharge and one month follow-up, we observed 16 (2.7%) non–CABG-related TIMI hemorrhagic complications including 5 (0.84%) major and 11 (1.8%) minor bleeds. Patients with bleeding had significantly lower post treatment values of ADP-induced aggregation (43±14% versus. 56±19%, P=0.002) and platelet reactivity index VASP (43±14% versus 54±23%; P=0.04) and a trend for lower values of arachidonic acid-induced aggregation (2.4±5.4 versus 13±21; P=0.27). After stratification by quartiles based on post treatment ADP-induced platelet aggregation, we identified patients in the first quartile as hyper-responders with very low post treatment platelet reactivity, below <40%. The risk of TIMI major and minor bleeding was significantly higher in the first quartile of hyper-responders than in the others quartiles: 10 (6.6%) versus 6 (1.4%), p=0.001.ConclusionOur results suggest that assessment of post treatment platelet reactivity might be used to detect hyper responders to antiplatelet therapy with higher risk of non-CABG related bleedings and tailor antiplatelet therapy according to both ischemic and bleeding risk

Sleep habits, academic performance, and the adolescent brain structure

Here we report the first and most robust evidence about how sleep habits are associated with regional brain grey matter volumes and school grade average in early adolescence. Shorter time in bed during weekdays, and later weekend sleeping hours correlate with smaller brain grey matter volumes in frontal, anterior cingulate, and precuneus cortex regions. Poor school grade average associates with later weekend bedtime and smaller grey matter volumes in medial brain regions. The medial prefrontal anterior cingulate cortex appears most tightly related to the adolescents' variations in sleep habits, as its volume correlates inversely with both weekend bedtime and wake up time, and also with poor school performance. These findings suggest that sleep habits, notably during the weekends, have an alarming link with both the structure of the adolescent brain and school performance, and thus highlight the need for informed interventions.Peer reviewe

Promiscuous scaffolds in proteins - non-native, non-additive and non-trivial

Publisher's version (útgefin grein)Promiscuity, the ability of an enzyme to catalyze diverse activities using the same active site, sets up the stage for the evolution of complex organisms through gene duplication and specialization. The detection of promiscuous motifs is crucial to understand the physiological relevance of a protein, or for any endeavor that intends to rationally modify these latent capabilities to design new proteins under laboratory conditions. We have established a methodology for identifying catalytic residues based on spatial and electrostatic congruence with known active site configurations. Here, we discuss insights gained in several initiatives using our method on different enzymes.Icelandic reasearch fund (RANNÍS) No. 141619Peer reviewe

Reward Versus Nonreward Sensitivity of the Medial Versus Lateral Orbitofrontal Cortex Relates to the Severity of Depressive Symptoms

BackgroundThe orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms.MethodsActivations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14.ResultsThe medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003).ConclusionsActivations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Peptidase activity of b-lactamases

Although b-lactamases have generally been considered as being devoid of peptidase activity, a low but significant hydrolysis of various N-acylated dipeptides was observed with representatives of each class of b-lactamases. The kcat/Km values were below 0.1 M-1·s-1, but the enzyme rate enhancement factors were in the range 5000–20000 for the best substrates. Not unexpectedly, the best 'peptidase' was the class C b-lactamase of Enterobacter cloacae P99, but, more surprisingly, the activity was always higher with the phenylacetyl- and benzoyl-D-Ala-D-Ala dipeptides than with the diacetyl- and a-acetyl-L-Lys-D-Ala-D-Ala tripeptides, which are the preferred substrates of the low-molecular-mass, soluble DD-peptidases. A comparison between the b-lactamases and DD-peptidases showed that it might be as difficult for a DD-peptidase to open the b-lactam ring as it is for the b-lactamases to hydrolyse the peptides, an observation which can be explained by geometric and stereoelectronic considerations

The right-handed parallel \u3b2-helix topology of Erwinia chrysanthemi pectin methylesterase Is intimately associated with both sequential folding and resistance to high pressure

The complex topologies of large multi-domain globular proteins make the study of their folding and assembly particularly demanding. It is often characterized by complex kinetics and undesired side reactions, such as aggregation. The structural simplicity of tandem-repeat proteins, which are characterized by the repetition of a basic structural motif and are stabilized exclusively by sequentially localized contacts, has provided opportunities for dissecting their folding landscapes. In this study, we focus on the Erwinia chrysanthemi pectin methylesterase (342 residues), an all-β pectinolytic enzyme with a right-handed parallel β-helix structure. Chemicals and pressure were chosen as denaturants and a variety of optical techniques were used in conjunction with stopped-flow equipment to investigate the folding mechanism of the enzyme at 25 °C. Under equilibrium conditions, both chemical- and pressure-induced unfolding show two-state transitions, with average conformational stability (ΔG° = 35 ± 5 kJ·mol−1) but exceptionally high resistance to pressure (Pm = 800 ± 7 MPa). Stopped-flow kinetic experiments revealed a very rapid (τ < 1 ms) hydrophobic collapse accompanied by the formation of an extended secondary structure but did not reveal stable tertiary contacts. This is followed by three distinct cooperative phases and the significant population of two intermediate species. The kinetics followed by intrinsic fluorescence shows a lag phase, strongly indicating that these intermediates are productive species on a sequential folding pathway, for which we propose a plausible model. These combined data demonstrate that even a large repeat protein can fold in a highly cooperative manner