Identification of dividing, determined sensory neuron precursors in the mammalian neural crest

Sensory and autonomic neurons of the vertebrate peripheral nervous system are derived from the neural crest. Here we use the expression of lineage-specific transcription factors as a means to identify neuronal subtypes that develop in rat neural crest cultures grown in a defined medium. Sensory neurons, identified by expression of the POU-domain transcription factor Brn-3.0, develop from dividing precursors that differentiate within 2 days following emigration from the neural tube. Most of these precursors generate sensory neurons even when challenged with BMP2, a factor that induces autonomic neurogenesis in many other cells in the explants. Moreover, BMP2 fails to prevent expression of the sensory-specific basic helix-loop-helix (bHLH) transcription factors neurogenin1, neurogenin2 and neuroD, although it induces expression of the autonomic-specific bHLH factor MASH1 and the paired homeodomain factor Phox2a in other cells. These data suggest that there are mitotically active precursors in the mammalian neural crest that can generate sensory neurons even in the presence of a strong autonomic-inducing cue. Further characterization of the neurons generated from such precursors indicates that, under these culture conditions, they exhibit a proprioceptive and/or mechanosensory, but not nociceptive, phenotype. Such precursors may therefore correspond to a lineally (Frank, E. and Sanes, J. (1991) Development 111, 895-908) and genetically (Ma, Q., Fode, C., Guillemot, F. and Anderson, D. J. (1999) Genes Dev. 13, in press) distinct subset of early-differentiating precursors of large-diameter sensory neurons identified in vivo

Speech recognition in noise for cochlear implant listeners: Benefits of residual hearing

The purpose of this study was to explore the potential advantages, both theoretical and applied, of preserving low-frequency acoustic hearing in cochlear implant patients. Several hypotheses are presented that predict that residual low-frequency acoustic hearing along with electric stimulation for high frequencies will provide an advantage over traditional long-electrode cochlear implants for the recognition of speech in competing backgrounds. A simulation experiment in normal-hearing subjects demonstrated a clear advantage for preserving low-frequency residual acoustic hearing for speech recognition in a background of other talkers, but not in steady noise. Three subjects with an implanted "short-electrode" cochlear implant and preserved low-frequency acoustic hearing were also tested on speech recognition in the same competing backgrounds and compared to a larger group of traditional cochlear implant users. Each of the three short-electrode subjects performed better than any of the traditional long-electrode implant subjects for speech recognition in a background of other talkers, but not in steady noise, in general agreement with the simulation studies. When compared to a subgroup of traditional implant users matched according to speech recognition ability in quiet, the short-electrode patients showed a 9-dB advantage in the multitalker background. These experiments provide strong preliminary support for retaining residual low-frequency acoustic hearing in cochlear implant patients. The results are consistent with the idea that better perception of voice pitch, which can aid in separating voices in a background of other talkers, was responsible for this advantage

An Estimation of Periconceptional Under-reporting of Dietary Energy Intake

Background The purpose of this cross-sectional study was to examine periconceptional misreporting of energy intake (EI) using the Willet food frequency questionnaire (WFFQ). Methods Women were recruited in the first trimester. Women completed a semi-quantitative WFFQ. Maternal body composition was measured using eight-electrode bioelectrical impedance analysis. Under-reporters were those whose ratio of EI to their calculated basal metabolic rate fell below the calculated plausible threshold for their physical activity category. Results The mean age was 30.1+5.3 years (n ¼ 524). The mean body mass index (BMI) was 25.4+5.6 kg/m2 , and 16.6% were obese (BMI 30.0 kg/m2 ). Under-reported EI was observed in 122 women (23.3%) with no over-reporters in the sample. Under-reporters were younger (P , 0.001), less likely to have a normal BMI (P ¼ 0.002) and more likely to be obese (P , 0.001) than plausible reporters. Under-reporters had higher percentage of body-fat and lower percentage of body fat-free mass (P , 0.001), were more likely to be at risk of relative deprivation (P ¼ 0.001) and reported a higher percentage of EI from carbohydrate (P ¼ 0.02) than plausible reporters. Conclusions Observed differences between under-reporters and plausible reporters suggest that the exclusion of these under-reporters represents an important potential source of bias in obesity research among women in the periconceptional period

Breast-feeding and Postpartum Maternal Weight Trajectories

We examined whether breast-feeding, and in particular exclusive breast-feeding, was associated with maternal weight and body composition changes at 4 months postpartum independently of other maternal variables

Maternal Nutrient Intakes From Food and Drinks Consumed in Early Pregnancy in Ireland

Background: The aim of this observational study was to measure food, macronutrient and micronutrient intakes of women presenting for antenatal care and assess compliance with current nutritional recommendations

Relationship between fasting plasma glucose levels and maternal food group and macronutrient intakes in pregnancy

Aim Increased maternal body mass index (BMI) has been consistently associated with elevated blood glucose levels during pregnancy. Studies to date investigating the relationship between maternal blood glucose levels and dietary intake have shown mixed results. We investigated the association between maternal fasting plasma glucose (FPG) levels and food group and macronutrient intakes in the first trimester of pregnancy, after adjustment for maternal bodyweight. Methods Women were recruited after sonographic confirmation of an ongoing singleton pregnancy in the first trimester. Dietary information was collected using the validated Willett Food Frequency Questionnaire. Maternal height and weight were measured and BMI calculated. Body composition was measured using advanced bioelectrical impedance analysis. FPG levels were obtained for women who were selectively screened with a 75 g oral glucose tolerance test. Results No associations were observed between maternal FPG levels and food group or macronutrient intakes but higher energy and starch intakes were found in obese subjects (P = 0.009 and P = 0.03 respectively). On univariate analysis, higher FPG levels were associated positively with higher maternal bodyweight, BMI, body fat, fat free mass and visceral fat (all P \u3c 0.001). However, on multivariate regression analysis, higher FPG levels remained associated only with maternal BMI \u3e 29.9 kg/m2 (OR 7.4, P = 0.01). Conclusions Our findings indicate that maternal BMI is the key determinant of maternal glycaemia. Interventions which focus on overall energy restriction and especially the limitation of dietary starch to optimise prepregnancy maternal bodyweight are likely to be useful in improving glycaemic control in higher risk pregnancies

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

Heightened distractibility is a core symptom of Attention Deficit Hyperactivity Disorder (ADHD). Effective treatment is normally with chronic orally administered psychostimulants including amphetamine.Treatment prevents worsening of symptoms but the site of therapeutic processes, and their nature, is unknown. Mounting evidence suggests that the superior colliculus (SC) is a key substrate in distractibility and a therapeutic target, so we assessed whether therapeutically-relevant changes are induced in this structure by chronic oral amphetamine. We hypothesized that amphetamine would alter visual responses and morphological measures. Six-week old healthy male rats were treated with oral amphetamine (2, 5 or 10 mg/kg) or a vehicle for one month after which local field potential and multiunit recordings were made from the superficial layers of the SC in response to whole-field light flashes in withdrawal. Rapid Golgi staining was also used to assess dendritic spines, and synaptophysin staining was used to assess synaptic integrity. Chronic amphetamine increased local field potential responses at higher doses, and increased synaptophysin expression, suggesting enhanced visual input involving presynaptic remodelling. No comparable increases in multiunit activity were found suggesting a mphetamine suppresses collicular output activity, counterbalancing the increased input. We also report,for the first time, five different dendritic spine types in the superficial layers and show these to be unaffected by amphetamine, indicating that suppression does not involve gross postsynaptic structural alterations. In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD

Cortisol interferes with the estradiol-induced surge of lutenizing hormone in the ewe

Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was &sim;1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge.<br /

Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling

Helminth infections are accompanied by eosinophilia in parasitized tissues. Eosinophils are effectors of immunity to tissue helminths. We previously reported that in the context of experimental filarial nematode infection, optimum tissue eosinophil recruitment was coordinated by local macrophage populations following IL-4R–dependent in situ proliferation and alternative activation. However, in the current study, we identify that control of chronic adult filarial worm infection is evident in IL-4Ra–deficient (IL-4Ra2/2) mice, whereby the majority of infections do not achieve patency. An associated residual eosinophilia was apparent in infected IL-4Ra2/2 mice. By treating IL-4Ra2/2 mice serially with anti-CCR3 Ab or introducing a compound deficiency in CCR3 within IL-4Ra2/2 mice, residual eosinophilia was ablated, and susceptibility to chronic adult Brugia malayi infection was established, promoting a functional role for CCR3-dependent eosinophil influx in immune control in the absence of IL-4/IL13–dependent immune mechanisms. We investigated additional cytokine signals involved in residual eosinophilia in the absence IL-4Ra signaling and defined that IL-4Ra2/2/IL-52/2 double-knockout mice displayed significant eosinophil deficiency compared with IL-4Ra2/2 mice and were susceptible to chronic fecund adult filarial infections. Contrastingly, there was no evidence that either IL-4R–dependent or IL-4R–independent/CCR3/IL-5–dependent immunity influenced B. malayi microfilarial loads in the blood. Our data demonstrate multiplicity of Th2-cytokine control of eosinophil tissue recruitment during chronic filarial infection and that IL-4R–independent/IL-5– and CCR3-dependent pathways are sufficient to control filarial adult infection via an eosinophil-dependent effector response prior to patency