Dynamics of the peripheral membrane protein P2 from human myelin measured by neutron scattering - a comparison between wild-type protein and a hinge mutant

Myelin protein P2 is a fatty acid-binding structural component of the myelin sheath in the peripheral nervous system, and its function is related to its membrane binding capacity. Here, the link between P2 protein dynamics and structure and function was studied using elastic incoherent neutron scattering (EINS). The P38G mutation, at the hinge between the β barrel and the α-helical lid, increased the lipid stacking capacity of human P2 in vitro, and the mutated protein was also functional in cultured cells. The P38G mutation did not change the overall structure of the protein. For a deeper insight into P2 structure-function relationships, information on protein dynamics in the 10 ps to 1 ns time scale was obtained using EINS. Values of mean square displacements mainly from protein H atoms were extracted for wild-type P2 and the P38G mutant and compared. Our results show that at physiological temperatures, the P38G mutant is more dynamic than the wild-type P2 protein, especially on a slow 1-ns time scale. Molecular dynamics simulations confirmed the enhanced dynamics of the mutant variant, especially within the portal region in the presence of bound fatty acid. The increased softness of the hinge mutant of human myelin P2 protein is likely related to an enhanced flexibility of the portal region of this fatty acid-binding protein, as well as to its interactions with the lipid bilayer surface requiring conformational adaptations

Does neuregulin-1 play a role in Type A behavior? The cardiovascular risk in young Finns study

BACKGROUND: Neuregulin-1 proteins are related to physiological correlates of Type A in terms of cardiac reactivity. Furthermore, neuregulin-1 gene (NRG1) may play a role in cardiovascular disease such as atherosclerosis and coronary heart disease i.e. the suggested "outcomes" of Type A behavior. Therefore, NRG1 is hypothesized to be associated with Type A behavior. METHODS: The study examined whether Type A behavior pattern is associated with the single nucleotide polymorphism (SNP) SNP8NRG221533 of the NRG1. The subjects were 631 men and women participating in the population-based Cardiovascular Risk in Young Finns study in 1992 and 2001. Type A was self-assessed with the Framingham Type A Scale and reassessed nine years later. RESULTS: Type A was associated with NRG1 genotype. Carriers of genotype CC scored lower on Type A compared to the others. CONCLUSION: Our study has pinpointed a SNP in NRG1 that predicts Type A behavior. As previous evidence suggests an association for NRG1 with beta-adrenergic stimulation, its role underlying Type A is discussed

Frequency of virus-resistant hosts determines experimental community dynamics.

Parasites, such as bacterial viruses (phages), can have large effects on host populations both at the ecological and evolutionary levels. In the case of cyanobacteria, phages can reduce primary production and infected hosts release intracellular nutrients influencing planktonic food web structure, community dynamics, and biogeochemical cycles. Cyanophages may be of great importance in aquatic food webs during large cyanobacterial blooms unless the host population becomes resistant to phage infection. The consequences on plankton community dynamics of the evolution of phage resistance in bloom forming cyanobacterial populations are still poorly studied. Here, we examined the effect of different frequencies of a phage-resistant genotype within a filamentous nitrogen-fixing Nodularia spumigena population on an experimental plankton community. Three Nodularia populations with different initial frequencies (0%, 5%, and 50%) of phage-resistant genotypes were inoculated in separate treatments with the phage 2AV2, the green alga Chlorella vulgaris, and the rotifer Brachionus plicatilis, which formed the experimental plankton community subjected to either nitrogen-limited or nitrogen-rich conditions. We found that the frequency of the phage-resistant Nodularia genotype determined experimental community dynamics. Cyanobacterial populations with a high frequency (50%) of the phage-resistant genotype dominated the cultures despite the presence of phages, retaining most of the intracellular nitrogen in the plankton community. In contrast, populations with low frequencies (0% and 5%) of the phage-resistant genotype were lysed and reduced to extinction by the phage, transferring the intracellular nitrogen held by Nodularia to Chlorella and rotifers, and allowing Chlorella to dominate the communities and rotifers to survive. This study shows that even though phages represent minuscule biomass, they can have key effects on community composition and eco-evolutionary feedbacks in plankton communities.Peer reviewe

Bankart versus Latarjet operation as a revision procedure after a failed arthroscopic Bankart repair

Background: An arthroscopic Bankart operation is the most common operative procedure to treat shoulder instability. In case of recurrence, both Bankart and Latarjet procedures are used as revision procedures. The purpose of this study was to compare the re-recurrence rate of instability and clinical results after arthroscopic revision Bankart and open revision Latarjet procedures following failed primary arthroscopic Bankart operations.Methods: Consecutive patients operatively treated for shoulder instability at Turku University Hospital between 2002 and 2013 were analyzed. Patients who underwent a primary arthroscopic Bankart operation followed by a recurrence of instability and underwent a subsequent arthroscopic Bankart or open Latarjet revision operation with a minimum of 1 year of follow-up were called in for a follow-up evaluation. The re-recurrence of instability, Subjective Shoulder Value, and Western Ontario Shoulder Instability index were assessed.Results: Of 69 patients, 48 (dropout rate, 30%) were available for follow-up. Recurrent instability symptoms occurred in 13 patients (43%) after the revision Bankart procedure and none after the revision Latarjet procedure. A statistically and clinically significant difference in the Western Ontario Shoulder Instability index was found between the patients after the revision Bankart and revision Latarjet operations (68% and 88%, respectively; P = .0166).Conclusions: The redislocation rate after an arthroscopic revision Bankart operation is high. Furthermore, patient-reported outcomes remain poor after a revision Bankart procedure compared with a revision Latarjet operation. We propose that in cases of recurring instability after a failed primary Bankart operation, an open Latarjet revision should be considered.</p

Dairy Intake and Body Composition and Cardiometabolic Traits among Adults : Mendelian Randomization Analysis of 182041 Individuals from 18 Studies

BACKGROUND: Associations between dairy intake and body composition and cardiometabolic traits have been inconsistently observed in epidemiological studies, and the causal relationship remains ill-defined. METHODS: We performed Mendelian randomization analysis using an established genetic variant located upstream of the lactase gene (LCT- 13910 C/T, rs4988235) associated with dairy intake as an instrumental variable (IV). The causal effects of dairy intake on body composition and cardiometabolic traits (lipids, glycemic traits, and inflammatory factors) were quantified by IV estimators among 182041 participants from 18 studies. RESULTS: Each 1 serving/day higher dairy intake was associated with higher lean mass [beta (SE) = 0.117 kg (0.035); P = 0.001], higher hemoglobin A(1c) [0.009% (0.002); P <0.001], lower LDL [-0.014 mmol/L (0.006); P = 0.013], total cholesterol (TC) [-0.012 mmol/L (0.005); P = 0.023], and non-HDL [- 0.012 mmol/L (0.005); P = 0.028]. The LCT- 13910 C/T CT + TT genotype was associated with 0.214 more dairy servings/day (SE = 0.047; P = 0.001), 0.284 cm higher waist circumference (SE = 0.118; P = 0.017), 0.112 kg higher lean mass (SE = 0.027; P = 3.8 X 10(-5)), 0.032 mmol/L lower LDL (SE = 0.009; P = 0.001), and 0.032 mmol/L lower TC (SE = 0.010; P = 0.001). Genetically higher dairy intake was associated with increased lean mass [0.523 kg per serving/day (0.170); P = 0.002] after correction for multiple testing (0.05/18). However, we find that genetically higher dairy intake was not associated with lipids and glycemic traits. CONCLUSIONS: The present study provides evidence to support a potential causal effect of higher dairy intake on increased lean mass among adults. Our findings suggest that the observational associations of dairy intake with lipids and glycemic traits may be the result of confounding. (C) 2019 American Association for Clinical ChemistryPeer reviewe

Childhood risk factors and carotid atherosclerotic plaque in adulthood : The Cardiovascular Risk in Young Finns Study

Background and aims: Carotid plaque is a specific sign of atherosclerosis and adults with carotid plaque are at increased risk for cardiovascular outcomes. Atherosclerosis has roots in childhood and pediatric guidelines provide cut-off values for cardiovascular risk factors. However, it is unknown whether these cut-offs predict adulthood advanced atherosclerosis. Methods: The Cardiovascular Risk in Young Finns Study is a follow-up of children that begun in 1980 when 2653 participants with data for the present analyses were aged 3-18 years. In 2001 and 2007 follow-ups, in addition to adulthood cardiovascular risk factors, carotid ultrasound data was collected. Long-term burden, as the area under the curve, was evaluated for childhood (6-18 years) risk factors. To study the associations of guideline-based cut-offs with carotid plaque, both childhood and adult risk factors were classified according to clinical practice guidelines. Results: Carotid plaque, defined as a focal structure of the arterial wall protruding into lumen > 50% compared to adjacent intima-media thickness, was present in 88 (3.3%) participants. Relative risk for carotid plaque, when adjusted for age and sex, was 3.03 (95% CI, 1.76-5.21) for childhood dyslipidemia, 1.51 (95% CI, 0.99-2.32) for childhood elevated systolic blood pressure, and 1.93 (95% CI, 1.26-2.94) for childhood smoking. Childhood dyslipidemia and smoking remained independent predictors of carotid plaque in models additionally adjusted for adult risk factors and family history of coronary heart disease. Carotid plaque was present in less than 1% of adults with no childhood risk factors. Conclusions: Findings reinforce childhood prevention efforts and demonstrate the utility of guideline-based cutoffs in identifying children at increased risk for adulthood atherosclerosis.Peer reviewe