The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation.

While aggregation-prone proteins are known to accelerate aging and cause age-related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG-4, SERF1A, and SERF2 have recently been identified as cellular modifiers of such proteotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with protein segments enriched in negatively charged and hydrophobic, aromatic amino acids. The absence of such segments, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid-promoting activity of SERF2. In protein aggregation models in the nematode worm Caenorhabditis elegans, protein aggregation and toxicity were suppressed by mutating the endogenous locus of MOAG-4 to neutralize charge. Our data indicate that MOAG-4 and SERF2 drive protein aggregation and toxicity by interactions with negatively charged segments in aggregation-prone proteins. Such charge interactions might accelerate primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our study points at charge interactions between cellular modifiers and amyloidogenic proteins as potential targets for interventions to reduce age-related protein toxicity

The LifeLines Cohort Study:Prevalence and treatment of cardiovascular disease and risk factors

AbstractBackgroundThe LifeLines Cohort Study is a large three-generation prospective study and Biobank. Recruitment and data collection started in 2006 and follow-up is planned for 30years. The central aim of LifeLines is to understand healthy ageing in the 21st century. Here, the study design, methods, baseline and major cardiovascular phenotypes of the LifeLines Cohort Study are presented.Methods and resultsBaseline cardiovascular phenotypes were defined in 9700 juvenile (8–18years) and 152,180 adult (≥18years) participants. Cardiovascular disease (CVD) was defined using ICD-10 criteria. At least one cardiovascular risk factor was present in 73% of the adult participants. The prevalence, adjusted for the Dutch population, was determined for risk factors (hypertension (33%), hypercholesterolemia (19%), diabetes (4%), overweight (56%), and current smoking (19%)) and CVD (myocardial infarction (1.8%), heart failure (1.0%), and atrial fibrillation (1.3%)). Overall CVD prevalence increased with age from 9% in participants<65years to 28% in participants≥65years. Of the participants with hypertension, hypercholesterolemia and diabetes, respectively 75%, 96% and 41% did not receive preventive pharmacotherapy.ConclusionsThe contemporary LifeLines Cohort Study provides researchers with unique and novel opportunities to study environmental, phenotypic, and genetic risk factors for CVD and is expected to improve our knowledge on healthy ageing. In this contemporary Western cohort we identified a remarkable high percentage of untreated CVD risk factors suggesting that not all opportunities to reduce the CVD burden are utilised

Expiratory Muscle Relaxation-Induced Ventilator Triggering: A Novel Patient-Ventilator Dyssynchrony

In critically ill patients receiving mechanical ventilation, expiratory muscles are recruited with high respiratory loading and/or low inspiratory muscle capacity. In this case report, we describe a previously unrecognized patient-ventilator dyssynchrony characterized by ventilator triggering by expiratory muscle relaxation, an observation that we termed expiratory muscle relaxation-induced ventilator triggering (ERIT). ERIT can be recognized with in-depth respiratory muscle monitoring as (1) an increase in gastric pressure (Pga) during expiration, resulting from expiratory muscle recruitment; (2) a drop in Pga (and hence, esophageal pressure) at the time of ventilator triggering; and (3) diaphragm electrical activity onset occurring after ventilator triggering. Future studies should focus on the incidence of ERIT and the impact in the patient receiving mechanical ventilation

Leidraad voor de psychosociale en leefstijlverkenning [binnen de aanpak Kind naar Gezonder Gewicht]:Vaststellen wat er speelt bij kind en gezin

Deze leidraad is bedoeld voor professionals die de rol van centrale zorgverlener vervullen. We geven achtergrondinformatie en we leggen uit hoe je de leidraad voor de psychosociale en leefstijlverkenning kunt gebruiken, welke vaardigheden daarbij belangrijk zijn en waaraan je verder nog kan denken

Replication Data for: Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in Phenylketonuria (PKU)

48 Homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice started dietary treatment on postnatal day 31 up to 10 months of age in the following six groups: WT control diet (WT C-HP), WT normal diet plus specific nutrient combination (WT SNC-HP), PKU normal diet (PKU C-HP), PKU normal diet plus specific nutrient combination (PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC-LP). Mice were tested three times (4,7, and 10 months) after treatment initiation during four behavioural tasks: open field (OF), novel object recognition task (NOR), spatial object recognition task (SOR), and balance beam task (BB). The results are stored in three zipped folders: Measurements.zip: Excel files with the results of the various behavioral tasks at 4, 7 and 10 months of age StatisticalAnalyses.zip: SPSS files (.sav) of the various behavioral tasks Neurotransmitters: Results and statistical analysis of the various neurotransmitter levels per mouse </ul

Replication Data for: Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in Phenylketonuria (PKU)

48 Homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice started dietary treatment on postnatal day 31 up to 10 months of age in the following six groups: WT control diet (WT C-HP), WT normal diet plus specific nutrient combination (WT SNC-HP), PKU normal diet (PKU C-HP), PKU normal diet plus specific nutrient combination (PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC-LP). Mice were tested three times (4,7, and 10 months) after treatment initiation during four behavioural tasks: open field (OF), novel object recognition task (NOR), spatial object recognition task (SOR), and balance beam task (BB). The results are stored in three zipped folders: Measurements.zip: Excel files with the results of the various behavioral tasks at 4, 7 and 10 months of age StatisticalAnalyses.zip: SPSS files (.sav) of the various behavioral tasks Neurotransmitters: Results and statistical analysis of the various neurotransmitter levels per mouse </ul