Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG

Curli are functional amyloid fibres that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria (predominantly of the α and γ classes). They provide a fitness advantage in pathogenic strains and induce a strong pro-inflammatory response during bacteraemia. Curli formation requires a dedicated protein secretion machinery comprising the outer membrane lipoprotein CsgG and two soluble accessory proteins, CsgE and CsgF. Here we report the X-ray structure of Escherichia coli CsgG in a non-lipidated, soluble form as well as in its native membrane-extracted conformation. CsgG forms an oligomeric transport complex composed of nine anticodon-binding-domain-like units that give rise to a 36-stranded β-barrel that traverses the bilayer and is connected to a cage-like vestibule in the periplasm. The transmembrane and periplasmic domains are separated by a 0.9-nm channel constriction composed of three stacked concentric phenylalanine, asparagine and tyrosine rings that may guide the extended polypeptide substrate through the secretion pore. The specificity factor CsgE forms a nonameric adaptor that binds and closes off the periplasmic face of the secretion channel, creating a 24,000 Å(3) pre-constriction chamber. Our structural, functional and electrophysiological analyses imply that CsgG is an ungated, non-selective protein secretion channel that is expected to employ a diffusion-based, entropy-driven transport mechanism

State of the world’s plants and fungi 2020

Kew’s State of the World’s Plants and Fungi project provides assessments of our current knowledge of the diversity of plants and fungi on Earth, the global threats that they face, and the policies to safeguard them. Produced in conjunction with an international scientific symposium, Kew’s State of the World’s Plants and Fungi sets an important international standard from which we can annually track trends in the global status of plant and fungal diversity

The diagnostic trajectory of developmental coordination disorder in the Netherlands : Experiences of mothers

Background Receiving a diagnosis can have a major impact on the child and its family. Parental satisfaction concerning the diagnostic trajectory is important with regard to acceptance and coping with their child's problems. Our aim was to describe the diagnostic trajectory of developmental coordination disorder (DCD) in the Netherlands and identify factors that are related to parents' satisfaction. Method Mothers of 60 children with a DCD diagnosis completed an online survey concerning their experiences during and after the diagnostic trajectory of obtaining this diagnosis. Results Forty percent of the mothers rated the diagnostic trajectory towards a DCD diagnosis as stressful and 47% rated the knowledgeability of the first professional they consulted (mostly a general practitioner, paediatric physical therapist, or youth health care physician) as having no or just superficial knowledge about DCD. Around 60% of the mothers described a lack of knowledge and support at their child's school after receiving the diagnosis. Notwithstanding this, the majority of the participating mothers was (very) satisfied with the diagnostic trajectory. Higher appreciation of both the manner of the diagnosing professional and the post-diagnostic support provided were predictive of higher satisfaction. Conclusions Our results underline the importance of improving the knowledgeability in primary schools and primary health care professionals with regard to DCD

Motor imagery training enhances motor skill in children with DCD: A replication study

Background Children with impaired motor coordination (or DCD) have difficulty using motor imagery. We have suggested that this difficulty is explained by the internal modeling deficit (IMD) hypothesis of DCD. Our previous training study lent support for this hypothesis by showing that a computerized imagery training protocol (involving action observation, and mental- and overt-rehearsal) was equally effective to perceptual-motor therapy (PMT) in promoting motor skill acquisition. Aims The study presented here was designed to replicate and extend this finding, targeting a select group of children with moderate-to-severe DCD. Methods and Procedures All 36 children with DCD who participated were referred to the study and scored below the 10th percentile for their age on the Movement Assessment Battery for Children (MABC). Using a randomized control trial, the referred children were assigned randomly to one of three groups using a blocked procedure: imagery training, perceptual-motor training (PMT), and wait-list control. Motor proficiency was measured using the MABC, pre and post-training. Individual training consisted of 60-min sessions, conducted once a week for 5 weeks. Results Results showed that the imagery protocol was equally effective as PMT in promoting motor skill acquisition, with moderate-to-large effect sizes. Individual differences showed that the majority of children in the two intervention groups improved their motor performance significantly. Conclusions Overall, these results further support the use of motor imagery protocols in the treatment of DCD, and tentative support for the IMD hypothesis. Developmental and dose issues in the implementation of imagery-based intervention are discussed

Feasibility of Motor Imagery Training for Children with Developmental Coordination Disorder – A Pilot Study

Children with Developmental Coordination Disorder (DCD) experience movement difficulties that may be linked to processes involved in motor imagery (MI). This paper discusses recent advances in theory that underpin the use of MI training for children with DCD. This knowledge is translated in a new MI training protocol which is compared with the cognitive orientation to daily occupational performance (CO-OP). Children meeting DSM-5 criteria for DCD were assigned to MI (n = 4) or CO-OP (n = 4) interventions and completed nine treatment sessions, including homework exercises. Results were positive, with two children in the MI group and three in the CO-OP group improving their m-ABC-2 score by ≥ 2 standard scores, interpreted as a clinically meaningful change. Moreover, all children and parents noticed improvements in motor skills after training. This is the first study to demonstrate the feasibility of a theoretically principled treatment protocol for MI training in children with DCD, and extends earlier work.Trial registration: The complete trial is registered at the Dutch trial register, www.trialregister.nl (NTR5471). http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=547

Motor imagery training for children with developmental coordination disorder: Study protocol for a randomized controlled trial

Contains fulltext : 151535.pdf (publisher's version ) (Open Access)Background: Previous studies have shown that the predictive control of movements is impaired in children with Developmental Coordination Disorder (DCD), most likely due to a deficit in the internal modeling of movements. Motor imagery paradigms have been used to test this internal modeling deficit. The aim of the present study is to examine whether a training focused on the mental imagery of motor skills, can help to improve the motor abilities of children with DCD. Methods/Design: A pre-post design will be used to examine the motor performance, motor imagery and motor planning abilities before and after a training of 9 weeks. Two groups will be included in this study (1) one receiving motor imagery (MI) training focused on the forward modeling of purposive actions, (2) one receiving Cognitive Orientation to daily Occupational Performance (CO-OP) training focused on identifying effective cognitive strategies that will increase motor competence. MI training will be given with the use of instruction videos of the motor skill that will be trained. Both groups will participate in 9 individual sessions of 45 min (once a week) with a paediatric physical or occupational therapist, added with homework sessions. Inclusion criteria are: (1) aged 7–12 years, (2) meeting the DSM-V criteria for DCD (motor performance substantially low (score on the m-ABC ≤ 16th percentile) and motor problems that interfere with daily life (DCDQ, and request for help at a paediatric physical or occupational therapist)). Exclusion criteria are IQ < 70 and other medical conditions causing the motor impairment. Discussion: The results of this study will help to make treatment protocols for children with DCD more evidence-based. This study will increase our knowledge about the efficacy of both the MI training and CO-OP training, and both children with DCD and therapists will benefit from this knowledge.9 p

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons