Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions.

Mucosal-Associated Invariant T (MAIT) cells are a population of innate T cells that play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine production. The metabolic and nutritional requirements for optimal MAIT cell effector responses are still emerging. Iron is an important micronutrient and is essential for cellular fitness, in particular cellular metabolism. Iron is also critical for many pathogenic microbes, including those that activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. These data collectively highlight the importance of a CD71-iron axis for human MAIT cell metabolism and functionality, an axis that may have implications in conditions where iron availability is limited.

Embedding key word sign prompts in a shared book reading activity: The impact on communication between children with Down syndrome and their parents.

BACKGROUND: Children with Down syndrome have speech and language difficulties that are disproportionate to their overall intellectual ability and relative strengths in the use of gesture. Shared book reading between parents and their children provides an effective context in which language development can be facilitated. However, children with Down syndrome often take a passive role in shared book reading and the use of key word signing (KWS) as a shared book reading technique has never been investigated. AIMS: This study aimed to compare children with Down syndrome's participation and use of KWS across two methods of shared book reading - one in which a book had key-word sign prompts embedded (signed condition) and the other in which a book was read as normal (unsigned condition). Measures of child and parent communicative behaviour were taken in each condition to establish if differences emerged. METHODS & PROCEDURES: A total of 36 children with Down syndrome (aged between 18 and 61 months) and their mothers took part in the study. Parent-child dyads were videoed at home reading two books, one in a signed and one in an unsigned condition. Child measures included total number of signs produced in each condition and levels of attention and initiation as measured by the Pivotal Behaviour Rating Scale. Parent measures included total number of utterances, mean length of utterance (MLU) in morphemes and vocabulary diversity (VOCD). Parental measures were transcribed using the Codes for Human Analysis Transcripts (CHAT) software and analysed by the Computerised Language Analysis software (CLAN). Contrasts in outcomes between the signed and unsigned conditions were estimated using Poisson and linear mixed-effects models, determined by the type of data. OUTCOMES & RESULTS: Results showed that children attempted to sign significantly more in the signed than unsigned condition, as well as showing significant increases in their levels of attention and initiation. There was also a significant increase in the total number of utterances used by parents in the signed versus unsigned condition and a decrease in MLU. VOCD was similar in both conditions. CONCLUSIONS & IMPLICATIONS: This study shows that the simple act of embedding key word signs into commercially available books, during shared book reading between parents and young children with Down syndrome, positively affects children's participation (initiation and attention) and use of KWS. The use of KWS as a core shared book reading technique may therefore be a fruitful avenue to facilitate growth in the language abilities of young children with Down syndrome. WHAT THIS PAPER ADDS: What is already known on this subject Most children with Down syndrome have significant speech and language difficulties, with relative strengths in the use of gesture. Shared book reading is an activity reported to positively affect language. However, children with Down syndrome are reported to take a passive role in shared book reading and are therefore more dependent on their parents to use techniques that facilitate their levels of participation, in order to maximise potential benefits. To the best of our knowledge, the communicative effects of embedding key word signing (KWS) in shared book reading have never been examined with children with Down syndrome. What this paper adds to existing knowledge This is the first study to investigate the communicative impact of parents embedding KWS in a shared book reading activity with their young children with Down syndrome. Our findings show that this relatively simple manipulation resulted in Increase in children's sign attempts. Increase in children's overall participation in shared book reading (indicated by levels of attention and initiation). Increase in the number of utterances produced by parents (primarily as a result of repetitions). Decrease in parental mean length of utterance. These findings suggest that embedding KWS in shared book reading is likely to facilitate increased language abilities in this cohort. What are the potential or actual clinical implications of this work? Shared book reading is part of the daily routine for many parents and their children with Down syndrome. Integrating KWS is a relatively simple adaptation to this activity which is likely to enhance children's language skills. Therapists can encourage parents to do this at home to support work carried out at school and in a clinical setting.

Tacrolimus restores the high- and low-pressure baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal injury rats.

NEW FINDINGS: What is the central question of this study? Does immunosuppression restore the baroreflex control of renal sympathetic nerve activity (RSNA) in an animal model of kidney injury? What is the main finding and its importance? Tacrolimus, a calcineurin inhibitor, restored the high- and low-pressure baroreflex control of RSNA following cisplatin-induced renal injury. ABSTRACT: Cisplatin administration causes depression of renal haemodynamic and excretory function and is associated with renal sympatho-excitation and loss of baroreflex regulation of renal sympathetic nerve activity (RSNA). This study investigated whether administration of the immunosuppressant tacrolimus in this cisplatin-mediated renal injury model could restore, or the acute intra-renal infusion of tumour necrosis factor α (TNF-α) could blunt, the high- or low-pressure baroreflex control of RSNA. Groups of control and cisplatin-treated (5 mg kg-1 , i.p. on day 0) rats received either saline or tacrolimus (0.25 mg kg-1  day-1 , i.p.) for 7 days prior to study. Rats were anaesthetised and prepared for measurement of mean arterial pressure (MAP), heart rate (HR) and RSNA. Baroreflex gain curves were generated and the degree of renal sympatho-inhibition determined (area under the curve (AUC) reported as %RSNA min) during acute volume expansion. Intrarenal TNF-α infusion (0.3 µg kg-1  h-1 ) in control rats decreased baroreflex gain by 32% (P < 0.05) compared to intra-renal saline infusion. In the cisplatin group (MAP: 98 ± 14 mmHg; HR: 391 ± 24beats min-1 ), the baroreflex gain for RSNA was 39% (P < 0.05) lower than that for the control group (MAP: 91 ± 7 mmHg; HR: 382 ± 29 beats min-1 ). In cisplatin-treated rats given daily tacrolimus (MAP: 84 ± 12 mmHg; HR: 357 ± 30 beats min-1 ), the baroreflex gain and renal sympatho-inhibition (AUC, 2440 ± 1071 vs. 635 ± 498% min) were restored to normal values. These findings provide evidence for the view that cisplatin administration initiates an injury involving inflammation which may contribute to the deranged baroreflex regulation of RSNA. This phenomenon appears mediated in part via the renal innervation.

Impact of Virtual Learning Environment on Students' Satisfaction, Engagement, Recall, and Retention.

BACKGROUND: Virtual learning environments (VLEs) were introduced to progress students from passive to active learners. Active learning promotes the critical thinking skills essential for the transfer/use of classroom-acquired knowledge into the clinical setting. A VLE forms an increasingly vital component of clinical skills development in a range of disciplines. MATERIAL AND METHODS: A randomized control trial was conducted with students randomly attending one of two teaching sessions about radiation therapy. Both sessions were identical except a VLE was used in the second talk with the first being solely didactic. Anonymous questionnaires were distributed. Two weeks after the talks, participants were required to complete the same knowledge questionnaire to determine retention. Mann-Whitney, means, standard deviations, and chi-squared tests were used according to data characteristics. Qualitative data (open-ended questions) were analysed thematically. RESULTS: Virtual learning seemed to significantly improve students' satisfaction/engagement and recall. A total of 40 students attended the teaching sessions. The student group taught using the VLE had higher mean scores for retention than the didactic group; however, this was not statistically significant. Use of VLEs was associated with greater satisfaction/engagement than didactic information (P = .003). Students' learning styles seemed to have no effect on their satisfaction/engagement and ease of learning. Three key themes emerged from the qualitative data: (1) the visuals were good/helpful, (2) the talk was informative, and (3) more details/visuals were required. DISCUSSION AND CONCLUSION: The key findings from this study suggest that there is a role for VLEs in the teaching of students. There is a need for the introduction of advanced technology into health care education as virtual reality, such as Virtual Environment of Radiotherapy, has shown improvement in students' satisfaction, engagement, and recall. Whether VLEs qualify students better than conventional didactic teaching is still undetermined, but these first results are encouraging.

Fasciola hepatica expresses multiple alpha- and beta-tubulin isotypes.

We have identified five alpha-tubulin and six beta-tubulin isotypes that are expressed in adult Fasciola hepatica. Amino acid sequence identities ranged between 72 and 95% for fluke alpha-tubulin and between 65 and 97% for beta-tubulin isotypes. Nucleotide sequence identity ranged between 68-77% and 62-80%, respectively, for their coding sequences. Phylogenetic analysis indicated that two of the alpha-tubulins and two of the beta-tubulins were distinctly divergent from the other trematode and nematode tubulin sequences described in this study, whereas the other isotypes segregated within the trematode clades. With regard to the proposed benzimidazole binding site on beta-tubulin, three of the fluke isotypes had tyrosine at position 200 of beta-tubulin, two had phenylalanine and one had leucine. All had phenylalanine at position 167 and glutamic acid at position 198. When isotype RT-PCR fragment sequences were compared between six individual flukes from the susceptible Cullompton isolate and from seven individual flukes from the two resistant isolates, Sligo and Oberon, these residues were conserved.

Tracing field hybridization in Ryegrass species using microsatellite and morphological markers.

We have assessed the utility of morphological and microsatellite markers for tracing field hybridization between Lolium multiflorum and Lolium perenne in cereal-enclosed gene flow plots. The presence of awns on the inflorescence of F(1) hybrids was found to be a reliable, but underscoring, indicator of L. multiflorum paternity in L. perenne derived seed as determined by inheritance of species-specific alleles at the microsatellite locus 'H01 H06' in these progeny. A positive correlation was evident in the experimental treatment between the number of pollen donor plants in a given plot and the frequency of hybrid F(1) seed harvested from pollen receptor plants in that plot. These experiments have established the utility of naturally occurring heritable markers for the measurement of gene flow rates in field Ryegrass populations, with particular significance for risk assessment modeling of potential gene flow from transgenic grass cultivars.