Distribution of the exfoliative toxin D gene in clinical Staphylococcus aureus isolates in France

Exfoliative toxin D (ETD) was identified recently as a new exfoliative toxin serotype. Like other exfoliative toxins, ETD induces intra-epidermal cleavage through the granular layer of the epidermis of neonatal mice. The distribution of ETD production was investigated in Staphylococcus aureus isolates from infected and colonised patients in France. The etd gene was found in 55 (10.5%) of 522 isolates tested. Isolates responsible for bullous impetigo and generalised staphylococcal scalded skin syndrome did not harbour etd, but etd was significantly more frequent in isolates causing cutaneous abscesses and furuncles. Most etd- and Panton-Valentine leukocidin-positive strains belonged to the clone of community-acquired methicillin-resistant S. aureus spreading currently throughout France.     

Forebrain structures specifically activated by conditioned taste aversion

This study investigates which forebrain structures show Fos protein expression during conditioned taste aversion (CTA) acquisition and whether Fos expression depends on the aversion strength. A novel taste paired with an intraperitoneal injection of a low dose of the malaise-inducing agent lithium chloride (LiCl) induced a weak CTA, whereas associating this novel taste with a high dose of LiCl induced a strong CTA. Increasing the strength of the gastric malaise alone enhanced Fos expression in central, basal, and lateral amygdala nuclei and decreased Fos expression in the nucleus accumbens core. Taste-malaise association induced specific Fos activation in the insular cortex (with both the low and the high doses of LiCl) and the nucleus accumbens shell (with the high LiCl dose only). No significant variation of Fos expression was measured in the perirhinal cortex. Several forebrain areas may be sites of taste-malaise convergence during CTA acquisition depending on the strength of the aversion.     

Outcome of acetylcholinesterase deficiency for neuromuscular functioning

Acetylcholinesterase (AChE) plays an essential role in neuromuscular transmission, therefore it is surprising that AChE knockout (KO) mice could live to the adulthood. Neuromuscular functioning in KO and normal (wild type, WT) mice were studied, at different age (1.5-, 4- and 9-month-old). Hindlimb muscle force productions in response to nerve or muscle electric stimulation were recorded in situ and in vitro. Our results show that contrary to WT mice, 1.5-, 4- and 9-month-old KO mice exhibited a decreased in tetanic force during short periods (500 ms) of repetitive nerve stimulations (tetanic fade). Nevertheless submaximal muscle forces in response to single or repetitive nerve stimulation were increased (potentiation) in 1.5-, 4- and 9-month-old KO mice as compared to WT mice (p<0.05). Tetanic fade and potentiation were absent when muscles were directly stimulated, indicating neuromuscular transmission alterations in KO mice. Contrary to younger mice, muscle weight and maximal tetanic force in response to repetitive nerve stimulation were not reduced in 4- and 9-month-old KO mice as compared to WT mice (p>0.05). In conclusion AChE deficit leads to marked neuromuscular alterations in hind limb muscle functioning and a prominent symptom is the lack of resistance to fatigue.     

Spontaneous B cell hyperactivity in autoimmune-prone MRL mice

The MRL-lpr/lpr mouse strain is a commonly used model of the human autoimmune disease systemic lupus erythematosus (SLE). Although much is known about the contribution of the lpr Fas mutation to B cell tolerance breakdown, the role of the genetic background of the MRL strain itself is less well explored. In this study, we use the MD4 anti-hen egg lysozyme Ig (IgHEL) transgenic system to explore B cell function in MRL+/+ and non-autoimmune mice. We demonstrate that MRL IgHEL B cells show spontaneous hyperactivity in the absence of self-antigen, which is associated with low total B cell numbers but an expansion of the marginal zone B cell population. However, B cell anergy is normal in the presence of soluble lysozyme [soluble hen egg lysozyme (sHEL)], and MRL IgHEL B cells undergo normal elimination in the presence of sHEL when competing with a polyclonal C57BL/6 B cell repertoire. We conclude that B cell hyperactivity may contribute to the autoimmune phenotype of MRL+/+ and MRL-lpr/lpr strains when it initiates antibody responses to rare or sequestered antigens that are below the threshold for tolerance induction, but that there is no B cell intrinsic defect in anergy in MRL mice.     

Effect of previous supramaximal work on lacticaemia during supra-anaerobic threshold exercise

Summary Twelve male and female subjects (eight trained, four untrained) exercised for 30 min on a treadmill at an intensity of maximal O₂ consumption (% O_2max) 90.0%, SD 4.7 greater than the anaerobic threshold of 4 mmol ·1^–1 (Th_an =83.6% O_2max, SD 8.9). Time-dependent changes in blood lactate concentration ([la_b]) during exercise occurred in two phases: the oxygen uptake ( O₂) transient phase (from 0 to 4 min) and the O₂ steady-state phase (4–30 min). During the transient phase, [la_b] increased markedly (l.30 mmol · l ^–1 · min ^–1, SD 0.13). During the steady-state phase, [la_b] increased slightly (0.02 mmol · 1^–1 · min^–1, SD 0.06) and when individual values were considered, it was seen that there were no time-dependent increases in [la_b] in half of the subjects. Following hyperlacticaemia (8.8 mmol -l^–1, SD 2.0) induced by a previous 2 min of supramaximal exercise (120% O_2max), [la_b] decreased during the O₂ transient (–0.118 mmol · 1^–1 · min^–1, SD 0.209) and steady-state (–0.088 mmol · 1^–1 · min ^–1, SD 0.103) phases of 30 min exercise (91.4% O_2max, SD 4.8). In conclusion, it was not possible from the Th_an to determine the maximal [la_b] steady state for each subject. In addition, lactate accumulated during previous supramaximal exercise was eliminated during the O₂ transient phase of exercise performed at an intensity above the Th_an. This effect is probably largely explained by the reduction in oxygen deficit during the transient phase. Under these conditions, the time-course of changes in [la_b] during the O₂ steady state was also affected.     

Game theoretical mapping of white matter contributions to visuospatial attention in stroke patients with hemineglect

White matter bundles linking gray matter nodes are key anatomical players to fully characterize associations between brain systems and cognitive functions. Here we used a multivariate lesion inference approach grounded in coalitional game theory (multiperturbation Shapley value analysis, MSA) to infer causal contributions of white matter bundles to visuospatial orienting of attention. Our work is based on the characterization of the lesion patterns of 25 right hemisphere stroke patients and the causal analysis of their impact on three neuropsychological tasks: line bisection, letter cancellation, and bells cancellation. We report that, out of the 11 white matter bundles included in our MSA coalitions, the optic radiations, the inferior fronto‐occipital fasciculus and the anterior cingulum were the only tracts to display task‐invariant contributions (positive, positive, and negative, respectively) to the tasks. We also report task‐dependent influences for the branches of the superior longitudinal fasciculus and the posterior cingulum. By extending prior findings to white matter tracts linking key gray matter nodes, we further characterize from a network perspective the anatomical basis of visual and attentional orienting processes. The knowledge about interactions patterns mediated by white matter tracts linking cortical nodes of attention orienting networks, consolidated by further studies, may help develop and customize brain stimulation approaches for the rehabilitation of visuospatial neglect.     

Regional mapping of the gene encoding dihydroorotate dehydrogenase,an enzyme involved in UMP synthesis,electron transport,and superoxide generation,to human chromosome region 16q22

De novo UMP synthesis is a critical metabolic pathway for nucleic acid synthesis and for a variety of metabolic pathways. The pathway is a target for many widely used cancer chemotherapy agents, several of which are pyrimidine analogs. Humans and cattle have been described with mutations in UMP synthesis that lead to serious inborn errors of metabolism. Dihydroorotate dehydrogenase (EC 1.3.3.1) (DHODH) carries out the fourth committed step in the pathway and may also be important for mitochondrial electron transport and oxygen radical metabolism. We report here that the gene encoding this enzyme in humans is located in the chromosomal region 16q22. With the mapping of DHODH, the mapping of all the steps of UMP synthesis is complete. All three genes involved map to different human chromosomes. This information is important in consideration of regulation of UMP synthesis in mammals, including humans.     

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population

Objective

To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population.

Methods

Thirty-patients were imaged at 3 T including DKI (K_app and D_app) with b-values 150/450/800/1150/1500 s/mm² and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics.

Results

Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and D_app were significantly lower and the K_app and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and D_app and higher K_app and MTR compared to normal PZ. MTR showed a moderate correlation to K_app (r = 0.570) and D_app (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825).

Conclusion

ADC, D_app, K_app and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease.

Key Points

? MTR was significantly higher in PZ and TZ tumours versus normal tissue ? K _app was significantly lower and D _app higher for PZ and TZ tumours ? There was no incremental value for DKI/MTI over mono-exponential ADC parameters ? No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease ? Divergent MTR/DKI values in TZ tumours suggests they offer different functional information