Temperature triggers immune evasion by Neisseria meningitidis.

Neisseria meningitidis has multiple strategies to evade complement-mediated killing, which contribute to its ability to cause septicaemic disease and meningitis. However, the meningococcus is primarily an obligate commensal of the human nasopharynx, and it is unclear why the bacterium has evolved exquisite mechanisms to avoid host immunity. Here we demonstrate that mechanisms of meningococcal immune evasion and resistance against complement increase in response to an elevation in ambient temperature. We have identified three independent RNA thermosensors located in the 5′-UTRs of genes necessary for capsule biosynthesis, the expression of factor H binding protein, and sialylation of lipopolysaccharide, which are essential for meningococcal resistance against immune killing(1,2). Therefore increased temperature (which occurs during inflammation) acts as a ‘danger signal’ for the meningococcus which enhances defence against human immune killing. Infection with viral pathogens, such as influenza, leads to inflammation in the nasopharynx with an elevated temperature and recruitment of immune effectors(3,4). Thermoregulation of immune defence could offer an adaptive advantage to the meningococcus during co-infection with other pathogens, and promote the emergence of virulence in an otherwise commensal bacterium

The transcription elongation factor NusA is required for stressinduced mutagenesis in Escherichia coli

Stress-induced mutagenesis describes the accumulation of mutations that occur in nongrowing cells, in contrast to mutagenesis that occurs in actively dividing populations, and has been referred to as stationary-phase or adaptive mutagenesis. The most widely studied system for stress-induced mutagenesis involves monitoring the appearance of Lac+ revertants of the strain FC40 under starvation conditions in Escherichia coli. The SOS-inducible translesion DNA polymerase DinB plays an important role in this phenomenon. Loss of DinB (DNA pol IV) function results in a severe reduction of Lac+ revertants. We previously reported that NusA, an essential component of elongating RNA polymerases, interacts with DinB. Here we report our unexpected observation that wild-type NusA function is required for stress-induced mutagenesis. We present evidence that this effect is unlikely to be due to defects in transcription of lac genes but rather is due to an inability to adapt and mutate in response to environmental stress. Furthermore, we extended our analysis to the formation of stress-induced mutants in response to antibiotic treatment, observing the same striking abolition of mutagenesis under entirely different conditions. Our results are the first to implicate NusA as a crucial participant in the phenomenon of stress-induced mutagenesis.National Institutes of Health (U.S.) (Grant CA21615)National Institute of Environmental Health Sciences (Grant P30 ES002109

Sense of entitlement to support for the reconciliation of employment and family life

This article explores young European women and men’s expectations of support - from the state and employers - for reconciling paid employment and family life. It is based on a qualitative study employing focus groups with young women and men in Norway, Sweden, Portugal, Ireland and the UK. Drawing on the concept of sense of entitlement, derived from social justice theory, it was expected that the type of welfare state and ‘gender contract’ that young adults have experienced will influence their sense of entitlement to support for work and family life. Findings indicate that participants perceived their entitlement to state and employer support differently across national context. However this is moderated by gender, parental and occupational status, and particularly by awareness of provisions in other countries in the case of state support, while perceived entitlement to employer support varies according to the specific policy considered, gender and perception of benefits to employers. Some implications for public policy makers and employers are discussed

Antibacterial and dermal toxicological profiles of ethyl acetate extract from Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae)

<p>Abstract</p> <p>Background</p> <p>The emergence in recent years of numerous resistant strains of pathogenic bacteria to a range of formerly efficient antibiotics constitutes a serious threat to public health. <it>Crassocephalum bauchiense</it>, a medicinal herb found in the West Region of Cameroon is used to treat gastrointestinal infections as well as liver disorders. The ethyl acetate extract from the leaves of <it>C. bauchiense </it>was evaluated for its antibacterial activity as well as acute and sub-acute toxicities.</p> <p>Methods</p> <p>The plant extract was prepared by maceration in ethyl acetate. Its phytochemical screening was done by standard methods. The broth microdilution method was used to evaluate the <it>in vitro </it>antibacterial activity. The <it>in vivo </it>antibacterial activity of a gel formulation (0.05, 1 and 2% w/v) of this extract was evaluated using a <it>Staphylococcus aureus</it>-induced dermatitis in a murine model. Selected haematological and biochemical parameters were used to evaluate the dermal sub-acute toxicity of the extract in rats.</p> <p>Results</p> <p>Phytochemical screening of the <it>C. bauchiense </it>extract revealed the presence of alkaloids, phenols, tannins and sterols. <it>In vitro </it>antibacterial activities were observed against all the tested microorganisms (MIC = 0.04-6.25 mg/ml). Formulated extract-gel (2% w/v) and gentamycin (reference drug) eradicated the microbial infection after five days of treatment. A single dermal dose of this extract up to 32 g/kg body weight (bw) did not produce any visible sign of toxicity. Also, daily dermal application of the <it>C. bauchiense </it>extract gel formulation for 28 days did not show any negative effect, instead some biochemical parameters such as alanine aminotransferase (ALT and AST), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides were significantly (p < 0.05) affected positively.</p> <p>Conclusion</p> <p>These results indicate that the <it>C. bauchiense </it>ethyl acetate extract can be used safely for the treatment of some bacterial infections.</p

Effect and process evaluation of a kindergarten-based, family-involved cluster randomised controlled trial in six European countries on four- to six-year-old children's steps per day: The ToyBox-study

Background: The ToyBox-intervention is a theory- and evidence-based intervention delivered in kindergartens to improve four- to six-year-old children''s energy balance-related behaviours and prevent obesity. The current study aimed to (1) examine the effect of the ToyBox-intervention on increasing European four- to six-year-old children'' steps per day, and (2) examine if a higher process evaluation score from teachers and parents was related to a more favourable effect on steps per day. Methods: A sample of 2438 four- to six-year-old children (51.9% boys, mean age 4.75±0.43years) from 6 European countries (Belgium, Bulgaria, Germany, Greece, Poland and Spain) wore a motion sensor (pedometer or accelerometer) for a minimum of two weekdays and one weekend day both at baseline and follow-up to objectively measure their steps per day. Kindergarten teachers implemented the physical activity component of the ToyBox-intervention for 6 weeks in total, with a focus on (1) environmental changes in the classroom, (2) the child performing the actual behaviour and (3) classroom activities. Children''s parents received newsletters, tip cards and posters. To assess intervention effects, multilevel repeated measures analyses were conducted for the total sample and the six intervention countries separately. In addition, process evaluation questionnaires were used to calculate a total process evaluation score (with implementation and satisfaction as a part of the overall score) for teachers and parents which was then linked with the physical activity outcomes. Results: No significant intervention effects on four- to six-year-old children'' steps per weekday, steps per weekend day and steps per average day were found, both in the total sample and in the country-specific samples (all p>0.05). In general, the intervention effects on steps per day were least favourable in four- to six-year-old children with a low teachers process evaluation score and most favourable in four- to six-year-old children with a high teachers process evaluation score. No differences in intervention effects were found for a low, medium or high parents'' process evaluation score. Conclusion: The physical activity component of the ToyBox-intervention had no overall effect on four- to six-year-old children'' steps per day. However, the process evaluation scores showed that kindergarten teachers that implemented the physical activity component of the ToyBox-intervention as planned and were satisfied with the physical activity component led to favourable effects on children''s steps per day. Strategies to motivate, actively involve and engage the kindergarten teachers and parents/caregivers are needed to induce larger effects

Differences in energy balance-related behaviours in European preschool children: The ToyBox-study

Background: The aim of the current study was to compare levels of energy balance-related behaviours (physical activity, sedentary behaviour, and dietary behaviours (more specifically water consumption, sugar-sweetened beverage consumption and unhealthy snacking)) in four- to six-year-old preschoolers from six European countries (Belgium, Bulgaria, Germany, Greece, Poland, and Spain) within the ToyBox cross-sectional study. Methods: A sample of 4,045 preschoolers (4.77 ± 0.43 years; 52.2% boys) had valid physical activity data (steps per day), parents of 8,117 preschoolers (4.78 ± 0.46 years; 53.0% boys) completed a parental questionnaire with questions on sedentary behaviours (television viewing, computer use, and quiet play), and parents of 7,244 preschoolers (4.77 ± 0.44 years; 52.0% boys) completed a food frequency questionnaire with questions on water consumption, sugar-sweetened beverage consumption and unhealthy snacking. Results: The highest levels of physical activity were found in Spain (12,669 steps/day on weekdays), while the lowest levels were found in Bulgaria and Greece (9,777 and 9,656 steps/day on weekdays, respectively). German preschoolers spent the least amount of time in television viewing (43.3 min/day on weekdays), while Greek preschoolers spent the most time in television viewing (88.5 min/day on weekdays). A considerable amount of time was spent in quiet play in all countries, with the highest levels in Poland (104.9 min/day on weekdays), and the lowest levels in Spain (60.4 min/day on weekdays). Belgian, German, and Polish preschoolers had the lowest intakes of water and the highest intakes of sugar-sweetened beverages. The intake of snacks was the highest in Belgian preschoolers (73.1 g/day) and the lowest in Greek preschoolers (53.3 g/day). Conclusions: Across six European countries, differences in preschoolers'' energy balance-related behaviours were found. Future interventions should target European preschoolers '' energy balance- related behaviours simultaneously, but should apply country-specific adaptations

Motor-Coordination-Dependent Learning, More than Others, Is Impaired in Transgenic Mice Expressing Pseudorabies Virus Immediate-Early Protein IE180

The cerebellum in transgenic mice expressing pseudorabies virus immediate-early protein IE180 (TgIE96) was substantially diminished in size, and its histoarchitecture was severely disorganized, resulting in severe ataxia. TgIE96 mice can therefore be used as an experimental model to study the involvement of cerebellar circuits in different learning tasks. The performance of three-month-old TgIE96 mice was studied in various behavioral tests, including associative learning (classical eyeblink conditioning), object recognition, spatial orientation (water maze), startle response and prepulse inhibition, and passive avoidance, and compared with that of wild-type mice. Wild-type and TgIE96 mice presented similar reflexively evoked eyeblinks, and acquired classical conditioned eyelid responses with similar learning curves for both trace and delay conditioning paradigms. The two groups of mice also had similar performances during the object recognition test. However, they showed significant differences for the other three tests included in this study. Although both groups of animals were capable of swimming, TgIE96 mice failed to learn the water maze task during the allowed time. The startle response to a severe tone was similar in both control and TgIE96 mice, but the latter were unable to produce a significant prepulse inhibition. TgIE96 mice also presented evident deficits for the proper accomplishment of a passive avoidance test. These results suggest that the cerebellum is not indispensable for the performance of classical eyeblink conditioning and for object recognition tasks, but seems to be necessary for the proper performance of water maze, prepulse inhibition, and passive avoidance tests