A dual-route account for access to grammatical gender: evidence from functional MRI

Research investigating the neural correlates of grammatical gender processing has provided contradictory evidence with respect to activation in the left inferior frontal gyrus (IFG). A possible account for these discrepancies is a dual-route model proposing explicit vs implicit access to the gender information. In this event-related fMRI experiment, we investigated this issue by taking into account different processing strategies reported by the subjects. The participants performed two tasks, a gender judgement of German nouns and a non-lexical baseline task (spacing of consonant letter strings). Depending on the reported strategy (silent production of the definite determiner or direct access to the gender information), different patterns of activation in the left IFG were observed. Direct access to gender information yielded activation in the inferior tip of BA 44, whereas the verbalisation strategy elicited activation in the superior portion of BA 44, BA 45/47, and the fronto-median wall. These results speak in favour of a dual-route account for modelling the access to grammatical gender information during language comprehension.     

Priming of Immunological Memory by Pneumococcal Conjugate Vaccine in Children Unresponsive to 23-Valent Polysaccharide Pneumococcal Vaccine

Pneumococcal polysaccharide vaccine (PPV) is of limited immunogenicity in infants and immunocompromised patients. Our prospective randomized controlled trial investigated whether priming with pneumococcal conjugate vaccine (PCV) induced specific immunological memory in previously nonresponders to PPV. Of a total of 33 children (2 to 18 years) with polysaccharide-specific immunodeficiency (PSI), group A (n = 16) received two doses of 7-valent PCV in a 4- to 6-week interval, and a booster dose of 23-valent PPV after one year. Group B (n = 17) received two doses of PPV in a 1-year interval exclusively. Specific antibody concentrations for serotypes 4, 5, 6B, 9V, 14, 18C, 19F, and 23F were determined (enzyme-linked immunosorbent assay) before and at 7 and 28 days after administration of the PPV booster and compared to an opsonophagocytosis assay. Of group A, 64 to 100% had antibody concentrations of ≥1 μg/ml on day 28 after the booster versus 25 to 94% of group B. Group A had significantly higher antibody concentrations for all PCV-containing serotypes already on day 7, indicating early memory response. Antibody concentrations were in accordance with functional opsonic activity, although opsonic titers varied among individuals. Pneumococcal vaccination was well tolerated. The incidence of airway infections was reduced after priming with PCV (10/year for group A versus 15/year for group B). Following a PPV booster, even patients primarily not responding to PPV showed a rapid and more pronounced memory response after priming with PCV.     

Failure to confirm influence of Methyltetrahydrofolate reductase (MTHFR) polymorphisms on age at onset of Huntington disease

Background  

Huntington disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Recently, suggestive association has been reported between a single nucleotide polymorphism (SNP; rs1801131, also known as A1298C) in the methyltetrahydrofolate reductase (MTHFR) gene and AO of HD. 5,10-MTHFR is a key enzyme in the folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using part of a previously established study cohort plus additional patients and appropriate statistical methods, we reinvestigated two polymorphisms in the MTHFR gene, C677T and A1298C, as well as their association with AO in 167 HD patients.     

Variability in acquired resistance of Pasteurella and Mannheimia isolates from the nasopharynx of calves, with particular reference to different herd types

To measure the level of antimicrobial resistance in potential bovine respiratory pathogens at different production types, nasal swabs were collected from 57 calves of 13 dairy herds, 150 calves of 9 beef cattle herds, and 289 calves of 5 high-density veal calf herds and investigated for the presence of Pasteurellaceae. All calves were less than 6 months old. Susceptibilities of the Pasteurella and Mannheimia isolates to eight antimicrobials were determined using an agar dilution method. P. multocida (37.3%) and hemolytic Mannheimia organisms (M. haemolytica sensu lato) (6.3%) were the most frequently detected organisms. The overall prevalence of isolates resistant to at least one antimicrobial from the dairy, beef, and veal calves were 17.6% (6/34), 21.9% (14/64), and 71.9% (64/89), respectively. In isolates obtained on the veal calf herds, acquired resistance to ampicillin, oxytetracycline, potentiated sulfonamides, gentamicin, tilmicosin, and enrofloxacin was frequently present, and 32.6% of these isolates were resistant to more than two of the tested antimicrobials. Resistance to ceftiofur and florfenicol was not detected. A substantial within-herd variability of species diversity and resistance profiles among isolates belonging to the genera Pasteurella and Mannheimia was found among the isolates of the veal calf farms.     

Discriminatory power and reproducibility of novel DNA typing methods for Mycobacterium tuberculosis complex strains

In recent years various novel DNA typing methods have been developed which are faster and easier to perform than the current internationally standardized IS6110 restriction fragment length polymorphism typing method. However, there has been no overview of the utility of these novel typing methods, and it is largely unknown how they compare to previously published methods. In this study, the discriminative power and reproducibility of nine recently described PCR-based typing methods for Mycobacterium tuberculosis were investigated using the strain collection of the interlaboratory study of Kremer et al. This strain collection contains 90 M. tuberculosis complex and 10 non-M. tuberculosis complex mycobacterial strains, as well as 31 duplicated DNA samples to assess reproducibility. The highest reproducibility was found with variable numbers of tandem repeat typing using mycobacterial interspersed repetitive units (MIRU VNTR) and fast ligation-mediated PCR (FLiP), followed by second-generation spoligotyping, ligation-mediated PCR (LM-PCR), VNTR typing using five repeat loci identified at the Queens University of Belfast (QUB VNTR), and the Amadio speciation PCR. Poor reproducibility was associated with fluorescent amplified fragment length polymorphism typing, which was performed in three different laboratories. The methods were ordered from highest discrimination to lowest by the Hunter-Gaston discriminative index as follows: QUB VNTR typing, MIRU VNTR typing, FLiP, LM-PCR, and spoligotyping. We conclude that both VNTR typing methods and FLiP typing are rapid, highly reliable, and discriminative epidemiological typing methods for M. tuberculosis and that VNTR typing is the epidemiological typing method of choice for the near future.     

TNF-R1 as a first trimester marker for prediction of pre-eclampsia

Objective: To examine whether the maternal serum concentration of the soluble receptor-1 of tumor necrosis factor-α (TNF-R1) at 11–13?+?6 weeks of gestation is a predictor of development of pre-eclampsia (PE).

Methods: This is a nested case–control study in which the concentration of TNF-R1 at 11?+?0 to 13?+?6 weeks was measured in 426 pregnant women in the first trimester. TNF-R1 values were expressed as multiples of the median (MoM) adjusted for maternal factors. The distributions of log TNF-R1 MoM in the control group and hypertensive disorders (early-PE [ePE], late-PE [lPE] and gestational hypertension [GH]) groups were compared. Logistic regression analysis was used to determine whether maternal factors, TNF-R1 or their combination make a significant contribution to the prediction of PE. Screening performance was determined by analysis of receiver–operating characteristics curves.

Results: Median concentration of TNF-R1 (ng/ml) was higher in ePE (2.62?±?0.67), lPE (2.12?±?0.56) and GH (2.19?±?0.45) compared to controls (2.04?±?0.42), p?=?0.001. Logistic regression analysis demonstrated that the addition of TNFR-1 to maternal factors did not make a significant contribution to the prediction of PE.

Conclusions: The maternal serum TNF-R1 concentration at 11–13?+?6 weeks of gestation was increased in pregnancies which developed hypertensive disorders, however, the addition of TNFR-1 did not improve the detection rate of these conditions compared with maternal factors alone.     

Embryology of the testicular descent

Numerous researchers studied the morphology of the testicular descent, including the possible function of the gubernaculum. However, a clear illustration of this process is still missing. The aim of this paper was to illustrate the embryology of the testicular descent in the rat by scanning electron microscopy. In a first phase of the intra-abdominal testicular descent, the testis moves actively from the lower pole of the kidney towards the bladder neck. In a second inguinal phase the testis enters groin and moves in the developing processus vaginalis peritonei caused by the disappearance of the bulb of the gubernaculums testis.     

Cerebral hemiatrophy associated with hippocampal sclerosis following a single prolonged febrile seizure

The etiological relation of prolonged febrile seizures with hippocampal sclerosis and cerebral hemiatrophy is controversial. Causal relationship is mainly adopted from retrospective statistical analysis and data from epilepsy surgery. We report a 17-month-old boy who had a prolonged febrile seizure with a transient postictal flaccid hemiparesis and anisocoria. Family history was unremarkable. Magnetic resonance imaging (MRI) revealed abnormal results in the right hippocampal area where diffusion-weighted sequences showed increased signal intensity consistent with acute neuronal edema. Repeat MRI 5 months later demonstrated sclerosis and atrophy of the right hippocampus in association with an increased T2-weighted signal and atrophy of the right frontal, temporal, and parietal lobe. In addition, 18-fluorodeoxyglucose positron emission tomography and 99mTc-ECD single-photon emission computed tomography revealed glucose hypometabolism and decreased perfusion in the right hemisphere, respectively. A final MRI, 12 months following the seizure, was widely unchanged. Interestingly, during a follow-up of 42 weeks, only minor motor deficits were observed. This case uniquely presents the acute onset of hippocampal sclerosis and, consecutively, cerebral hemiatrophy after a single febrile seizure. This suggests that a single prolonged febrile seizure may cause global morphological changes of the brain, not only affecting hippocampal formation.     

LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus

Cellular attachment factors like the C-type lectins DC-SIGN and DC-SIGNR (collectively referred to as DC-SIGN/R) can augment viral infection and might promote viral dissemination in and between hosts. The lectin LSECtin is encoded in the same chromosomal locus as DC-SIGN/R and is coexpressed with DC-SIGNR on sinusoidal endothelial cells in liver and lymphnodes. Here, we show that LSECtin enhances infection driven by filovirus glycoproteins (GP) and the S protein of SARS coronavirus, but does not interact with human immunodeficiency virus type-1 and hepatitis C virus envelope proteins. Ligand binding to LSECtin was inhibited by EGTA but not by mannan, suggesting that LSECtin unlike DC-SIGN/R does not recognize high-mannose glycans on viral GPs. Finally, we demonstrate that LSECtin is N-linked glycosylated and that glycosylation is required for cell surface expression. In summary, we identified LSECtin as an attachment factor that in conjunction with DC-SIGNR might concentrate viral pathogens in liver and lymph nodes.     

Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome

Defects of mitochondrial polymerase gamma (POLG) underlie neurological diseases ranging from myopathies to parkinsonism and infantile Alpers syndrome. The most severe manifestations have been associated with mutations of the 'spacer' region of POLG, the function of which has remained unstudied in humans. We identified a family, segregating three POLG amino acid variants, A467T, R627Q and Q1236H. The first two affect the spacer region and the third is a polymorphism, allelic with R627Q. Three grades of disease severity appeared to correlate with the genotypes. The patient with the most severe outcome, cerebellar ataxia syndrome, had all three variants, those with R627Q and Q1236H had juvenile-onset ptosis and gait disturbance and those with a single A467T allele had late-onset ptosis. To evaluate the molecular pathogenesis of these spacer defects, we expressed and purified the mutant proteins and studied their catalytic properties in vitro. The A467T substitution resulted in clearly decreased activity, DNA binding and processivity of the polymerase. Our biochemical data, the dominant manifestation of A467T and its previously reported high frequency in the Belgian population (0.6%), emphasize the role of this mutation as a common cause of neurological disease. Further, biochemical evidence that a polymorphic variant may modify the function of a mutant POLG, if occurring in the same polypeptide, is shown here. Finally, and surprisingly, other pathogenic spacer mutants showed DNA-binding affinities and processivities similar to or higher than the controls, suggesting that the disease-causing mechanisms of spacer mutations extend beyond the basic catalytic functions of POLG.