Gymnemic acids inhibit hyphal growth and virulence in Candida albicans

Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine

Nuclear and Chloroplast Microsatellites Show Multiple Introductions in the Worldwide Invasion History of Common Ragweed, Ambrosia artemisiifolia

BACKGROUND: Ambrosia artemisiifolia is a North American native that has become one of the most problematic invasive plants in Europe and Asia. We studied its worldwide population genetic structure, using both nuclear and chloroplast microsatellite markers and an unprecedented large population sampling. Our goals were (i) to identify the sources of the invasive populations; (ii) to assess whether all invasive populations were founded by multiple introductions, as previously found in France; (iii) to examine how the introductions have affected the amount and structure of genetic variation in Europe; (iv) to document how the colonization of Europe proceeded; (v) to check whether populations exhibit significant heterozygote deficiencies, as previously observed. PRINCIPAL FINDINGS: We found evidence for multiple introductions of A. artemisiifolia, within regions but also within populations in most parts of its invasive range, leading to high levels of diversity. In Europe, introductions probably stem from two different regions of the native area: populations established in Central Europe appear to have originated from eastern North America, and Eastern European populations from more western North America. This may result from differential commercial exchanges between these geographic regions. Our results indicate that the expansion in Europe mostly occurred through long-distance dispersal, explaining the absence of isolation by distance and the weak influence of geography on the genetic structure in this area in contrast to the native range. Last, we detected significant heterozygote deficiencies in most populations. This may be explained by partial selfing, biparental inbreeding and/or a Wahlund effect and further investigation is warranted. CONCLUSIONS: This insight into the sources and pathways of common ragweed expansion may help to better understand its invasion success and provides baseline data for future studies on the evolutionary processes involved during range expansion in novel environments

Cell cycle-independent phospho-regulation of Fkh2 during hyphal growth regulates Candida albicans pathogenesis.

The opportunistic human fungal pathogen, Candida albicans, undergoes morphological and transcriptional adaptation in the switch from commensalism to pathogenicity. Although previous gene-knockout studies have identified many factors involved in this transformation, it remains unclear how these factors are regulated to coordinate the switch. Investigating morphogenetic control by post-translational phosphorylation has generated important regulatory insights into this process, especially focusing on coordinated control by the cyclin-dependent kinase Cdc28. Here we have identified the Fkh2 transcription factor as a regulatory target of both Cdc28 and the cell wall biosynthesis kinase Cbk1, in a role distinct from its conserved function in cell cycle progression. In stationary phase yeast cells 2D gel electrophoresis shows that there is a diverse pool of Fkh2 phospho-isoforms. For a short window on hyphal induction, far before START in the cell cycle, the phosphorylation profile is transformed before reverting to the yeast profile. This transformation does not occur when stationary phase cells are reinoculated into fresh medium supporting yeast growth. Mass spectrometry and mutational analyses identified residues phosphorylated by Cdc28 and Cbk1. Substitution of these residues with non-phosphorylatable alanine altered the yeast phosphorylation profile and abrogated the characteristic transformation to the hyphal profile. Transcript profiling of the phosphorylation site mutant revealed that the hyphal phosphorylation profile is required for the expression of genes involved in pathogenesis, host interaction and biofilm formation. We confirmed that these changes in gene expression resulted in corresponding defects in pathogenic processes. Furthermore, we identified that Fkh2 interacts with the chromatin modifier Pob3 in a phosphorylation-dependent manner, thereby providing a possible mechanism by which the phosphorylation of Fkh2 regulates its specificity. Thus, we have discovered a novel cell cycle-independent phospho-regulatory event that subverts a key component of the cell cycle machinery to a role in the switch from commensalism to pathogenicity

Perceptual modification of the built environment to influence behaviour associated with physical activity: Quasi-experimental field studies of a stair banister illusion

Re-engineering the built environment to influence behaviours associated with physical activity potentially provides an opportunity to promote healthier lifestyles at a population level. Here we present evidence from two quasi-experimental field studies in which we tested a novel, yet deceptively simple, intervention designed to alter perception of, and walking behaviour associated with, stairs in an urban area. Objectives. To examine whether stair banister adjustment has an influence on perceptions of stair steepness or on walking behaviour when approaching the stairs. Methods. In Study 1, we asked participants (n=143) to visually estimate the steepness of a set of stairs viewed from the top, when the stair banister was adjusted so that it converged with or diverged from the stairs (±1.91º) or remained neutral (±0º). In Study 2, the walking behaviour of participants (n=36) was filmed as they approached the stairs to descend, unaware that the banister converged, diverged or was neutral. Results. In Study 1, participants estimated the stairs to be steeper if the banister diverged from rather than converged with the stairs. The effect was greater when participants were unaware of the adjustment. In Study 2, walking speed was significantly slower when the banister diverged from rather than converged with the stairs. Conclusions. These findings encourage us to speculate about the potential to economically re-engineer features of the built environment in order to provide opportunities for action (affordances) that invite physical activity behaviour or even promote safer navigation of the environment

Is implicit motor learning preserved after stroke? A systematic review with meta-analysis

© 2016 Kal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Many stroke patients experience difficulty with performing dual-tasks. A promising intervention to target this issue is implicit motor learning, as it should enhance patients' automaticity of movement. Yet, although it is often thought that implicit motor learning is preserved poststroke, evidence for this claim has not been systematically analysed yet. Therefore, we systematically reviewed whether implicit motor learning is preserved post-stroke, and whether patients benefit more from implicit than from explicit motor learning. We comprehensively searched conventional (MEDLINE, Cochrane, Embase, PEDro, PsycINFO) and grey literature databases (BIOSIS, Web of Science, OpenGrey, British Library, trial registries) for relevant reports. Two independent reviewers screened reports, extracted data, and performed a risk of bias assessment. Overall, we included 20 out of the 2177 identified reports that allow for a succinct evaluation of implicit motor learning. Of these, only 1 study investigated learning on a relatively complex, whole-body (balance board) task. All 19 other studies concerned variants of the serial-reaction time paradigm, with most of these focusing on learning with the unaffected hand (N = 13) rather than the affected hand or both hands (both: N = 4). Four of the 20 studies compared explicit and implicit motor learning post-stroke. Meta-analyses suggest that patients with stroke can learn implicitly with their unaffected side (mean difference (MD) = 69 ms, 95% CI[45.1, 92.9], p < .00001), but not with their affected side (standardized MD = -.11, 95% CI[-.45, .25], p = .56). Finally, implicit motor learning seemed equally effective as explicit motor learning post-stroke (SMD = -.54, 95% CI[-1.37, .29], p = .20). However, overall, the high risk of bias, small samples, and limited clinical relevance of most studies make it impossible to draw reliable conclusions regarding the effect of implicit motor learning strategies post-stroke. High quality studies with larger samples are warranted to test implicit motor learning in clinically relevant contexts

A multicentric study of the G.E.T.T.E.C. (Groupe d’Etudes des Tumeurs de la Tête et du Cou) about 408 clinically complete responders after neo-adjuvant chemotherapy for head and neck carcinomas

info:eu-repo/semantics/publishe