DC activated via dectin-1 convert Treg into IL-17 producers

Th cells producing IL-17 play a pro-inflammatory role at mucosal surfaces. Treg at the same sites dampen inflammation and prevent immunopathology. Th cells producing IL-17 (Th17) and Treg are thought to be distinct populations defined by expression of the transcription factors ROR-γt and Foxp3, respectively. Here, we show that mouse CD25+Foxp3+ Treg can be converted into a hybrid T-cell population characterized by the expression of Foxp3 and ROR-γt and the production of IL-17. Conversion was observed upon coculture with DC selectively activated via dectin-1, a C-type lectin receptor involved in fungal recognition, and depended on IL-23 produced by DC. Within the Foxp3+ population, only Foxp3+ROR-γt+ T cells but not Foxp3+ROR-γt−–T cells become Foxp3+IL-17+ T cells. These results indicate that some Foxp3+ T cells can produce IL-17 while retaining Foxp3 expression and suggest that Treg could play an unexpected pro-inflammatory role in some settings

Connectivity between mPFC and PCC predicts post‐choice attitude change: The self‐referential processing hypothesis of choice justification

Prior research shows that after making a choice, decision makers shift their attitudes in a choice‐congruous direction. Although this post‐choice attitude change effect is robust, the neural mechanisms underlying it are poorly understood. Here, we tested the hypothesis that decision makers elaborate on their choice in reference to self‐knowledge to justify the choice they have made. This self‐referential processing of the choice is thought to play a pivotal role in the post‐choice attitude change. Twenty‐four young American adults made a series of choices. They also rated their attitudes toward the choice options before and after the choices. In support of the current hypothesis, we found that changes in functional connectivity between two putative self‐regions (medial prefrontal cortex and posterior cingulate cortex/precuneus]) during the post‐choice (vs. pre‐choice) rating of the chosen options predicted the post‐choice shift of the attitudes toward the chosen options. This finding is the first to suggest that cognitive integration of various self‐relevant cognitions is instrumental in fostering post‐choice attitude change. Hum Brain Mapp 37:3810–3820, 2016. © 2016 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134093/1/hbm23277_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134093/2/hbm23277.pd

Organic Photovoltaic Cells: From Performance Improvement to Manufacturing Processes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111806/1/smll201402883.pd

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Genetic Metabolic Complementation establishes a requirement for GDP-fucose in <i>Leishmania</i>

To survive in its sand fly vector, the trypanosomatid protozoan parasite Leishmania first attaches to the midgut to avoid excretion, but eventually it must detach for transmission by the next bite. In Leishmania major strain Friedlin, this is controlled by modifications of the stage-specific adhesin lipophosphoglycan (LPG). During differentiation to infective metacyclics, d-arabinopyranose (d-Arap) caps the LPG side-chain galactose residues, blocking interaction with the midgut lectin PpGalec, thereby leading to parasite detachment and transmission. Previously, we characterized two closely related L. major genes (FKP40 and AFKP80) encoding bifunctional proteins with kinase/pyrophosphorylase activities required for salvage and conversion of l-fucose and/or d-Arap into the nucleotide-sugar substrates required by glycosyltransferases. Whereas only AFKP80 yielded GDP-d-Arap from exogenous d-Arap, both proteins were able to salvage l-fucose to GDP-fucose. We now show that Δafkp80− null mutants ablated d-Arap modifications of LPG as predicted, whereas Δfkp40− null mutants resembled wild type (WT). Fucoconjugates had not been reported previously in L. major, but unexpectedly, we were unable to generate fkp40−/afkp80− double mutants, unless one of the A/FKPs was expressed ectopically. To test whether GDP-fucose itself was essential for Leishmania viability, we employed “genetic metabolite complementation.” First, the trypanosome de novo pathway enzymes GDP-mannose dehydratase (GMD) and GDP-fucose synthetase (GMER) were expressed ectopically; from these cells, the Δfkp40−/Δafkp80− double mutant was now readily obtained. As expected, the Δfkp40−/Δafkp80−/+TbGMD-GMER line lacked the capacity to generate GDP-Arap, while synthesizing abundant GDP-fucose. These results establish a requirement for GDP-fucose for L. major viability and predict the existence of an essential fucoconjugate(s)

ω-3 Fatty acids for major depressive disorder in adults: an abridged Cochrane review.

OBJECTIVE: To assess the effects of n-3 polyunsaturated fatty acids (n-3PUFAs; also known as ω-3 fatty acids) compared with comparator for major depressive disorder (MDD) in adults. DESIGN: Systematic review and meta-analyses. DATA SOURCES: The Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Registers (CCDANCTR) and International Trial Registries searched to May 2015. CINAHL searched to September 2013. TRIAL SELECTION: INCLUSION CRITERIA: a randomised controlled trial (RCT); that provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and was conducted in adults with MDD. OUTCOMES: Primary outcomes were depressive symptomology and adverse events. RESULTS: 20 trials encompassing 26 relevant studies were found. For n-3PUFAs versus placebo, n-3PUFA supplementation resulted in a small-to-modest benefit for depressive symptomology: SMD=-0.32 (95% CI -0.52 to -0.12; 25 studies, 1373 participants, very low-quality evidence), but this effect is unlikely to be clinically meaningful, is very imprecise and, based on funnel plot inspection, sensitivity analyses and comparison with large well-conducted trials, is likely to be biased. Considerable evidence of heterogeneity between studies was also found, and was not explained by subgroup or sensitivity analyses. Numbers of individuals experiencing adverse events were similar in intervention and placebo groups (OR=1.24, 95% CI 0.95 to 1.62; 19 studies, 1207 participants; very low-quality evidence). For n-3PUFAs versus antidepressants, no differences were found between treatments in depressive symptomology (MD=-0.70 (95% CI -5.88 to 4.48); 1 study, 40 participants, very low-quality evidence). CONCLUSIONS: At present, we do not have sufficient evidence to determine the effects of n-3PUFAs as a treatment for MDD. Further research in the form of adequately powered RCTs is needed

The association of Alu repeats with the generation of potential AU-rich elements (ARE) at 3' untranslated regions.

BACKGROUND: A significant portion (about 8% in the human genome) of mammalian mRNA sequences contains AU (Adenine and Uracil) rich elements or AREs at their 3' untranslated regions (UTR). These mRNA sequences are usually stable. However, an increasing number of observations have been made of unstable species, possibly depending on certain elements such as Alu repeats. ARE motifs are repeats of the tetramer AUUU and a monomer A at the end of the repeats ((AUUU)(n)A). The importance of AREs in biology is that they make certain mRNA unstable. Proto-oncogene, such as c-fos, c-myc, and c-jun in humans, are associated with AREs. Although it has been known that the increased number of ARE motifs caused the decrease of the half-life of mRNA containing ARE repeats, the exact mechanism is as of yet unknown. We analyzed the occurrences of AREs and Alu and propose a possible mechanism for how human mRNA could acquire and keep AREs at its 3' UTR originating from Alu repeats. RESULTS: Interspersed in the human genome, Alu repeats occupy 5% of the 3' UTR of mRNA sequences. Alu has poly-adenine (poly-A) regions at its end, which lead to poly-thymine (poly-T) regions at the end of its complementary Alu. It has been found that AREs are present at the poly-T regions. From the 3' UTR of the NCBI's reference mRNA sequence database, we found nearly 40% (38.5%) of ARE (Class I) were associated with Alu sequences (Table 1) within one mismatch allowance in ARE sequences. Other ARE classes had statistically significant associations as well. This is far from a random occurrence given their limited quantity. At each ARE class, random distribution was simulated 1,000 times, and it was shown that there is a special relationship between ARE patterns and the Alu repeats. CONCLUSION: AREs are mediating sequence elements affecting the stabilization or degradation of mRNA at the 3' untranslated regions. However, AREs' mechanism and origins are unknown. We report that Alu is a source of ARE. We found that half of the longest AREs were derived from the poly-T regions of the complementary Alu

Effects of aversive odour presentation on inhibitory control in the Stroop colour-word interference task

<p>Abstract</p> <p>Background</p> <p>Due to the unique neural projections of the olfactory system, odours have the ability to directly influence affective processes. Furthermore, it has been shown that emotional states can influence various non-emotional cognitive tasks, such as memory and planning. However, the link between emotional and cognitive processes is still not fully understood. The present study used the olfactory pathway to induce a negative emotional state in humans to investigate its effect on inhibitory control performance in a standard, single-trial manual Stroop colour-word interference task. An unpleasant (H₂S) and an emotionally neutral (Eugenol) odorant were presented in two separate experimental runs, both in blocks alternating with ambient air, to 25 healthy volunteers, while they performed the cognitive task.</p> <p>Results</p> <p>Presentation of the unpleasant odorant reduced Stroop interference by reducing the reaction times for incongruent stimuli, while the presentation of the neutral odorant had no effect on task performance.</p> <p>Conclusions</p> <p>The odour-induced negative emotional state appears to facilitate cognitive processing in the task used in the present study, possibly by increasing the amount of cognitive control that is being exerted. This stands in contrast to other findings that showed impaired cognitive performance under odour-induced negative emotional states, but is consistent with models of mood-congruent processing.</p

Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis

Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Published versio

Real-Time, Real World Learning—Capitalising on Mobile Technology

This chapter explores the adoption of Web 2.0 technologies to promote active learning by students and to both mediate and enhance classroom instruction. Web 2.0 refers to open source, web-enabled applications (apps) that are driven by user-manipulated and user-generated content (Kassens-Noor, 2012). These apps are often rich in user participation, have dynamic content, and harness the collective intelligence of users (Chen, Hwang, & Wang, 2012). As such, these processes create “active, context based, personalised learning experiences” (Kaldoudi, Konstantinidis, & Bamidis, 2010, p. 130) that prioritise learning ahead of teaching. By putting the learner at the centre of the education process educators can provide environments that enhance employability prospects and spark a passion for learning that, hopefully, lasts a lifetime. As such, we critique an active learning approach that makes use of technology such as mobile applications (apps), Twitter, and augmented reality to enhance students’ real world learning. Dunlap and Lowenthal (2009) argue that social media can facilitate active learning as they recreate informal, free-flowing communications that allow students and academics to connect on a more emotional level. Furthermore, their use upskills students in the technical complexities of the digital world and also the specialised discourses that are associated with online participation, suitable for real world learning and working (Fig. 16.1). Three case studies explore the benefits of Web 2.0 processes. The first details the use of Twitter chats to connect students, academics, and industry professionals via online synchronous discussions that offer a number of benefits such as encouraging concise writing from students and maintaining on-going relationships between staff, students, and industry contacts. The second details a location-based mobile app that delivers content to students when they enter a defined geographical boundary linked to an area of a sports precinct. Finally, we explore the use of augmented reality apps to enhance teaching in Human Geography and Urban Studies