Phosphorylation by the stress-activated MAPK Slt2 down-regulates the yeast TOR complex 2

Saccharomyces cerevisiae target of rapamycin (TOR) complex 2 (TORC2) is an essential regulator of plasma membrane lipid and protein homeostasis. How TORC2 activity is modulated in response to changes in the status of the cell envelope is unclear. Here we document that TORC2 subunit Avo2 is a direct target of Slt2, the mitogen-activated protein kinase (MAPK) of the cell wall integrity pathway. Activation of Slt2 by overexpression of a constitutively active allele of an upstream Slt2 activator (Pkc1) or by auxin-induced degradation of a negative Slt2 regulator (Sln1) caused hyperphosphorylation of Avo2 at its MAPK phosphoacceptor sites in a Slt2-dependent manner and diminished TORC2-mediated phosphorylation of its major downstream effector, protein kinase Ypk1. Deletion of Avo2 or expression of a phosphomimetic Avo2 allele rendered cells sensitive to two stresses (myriocin treatment and elevated exogenous acetic acid) that the cell requires Ypk1 activation by TORC2 to survive. Thus, Avo2 is necessary for optimal TORC2 activity, and Slt2-mediated phosphorylation of Avo2 down-regulates TORC2 signaling. Compared with wild-type Avo2, phosphomimetic Avo2 shows significant displacement from the plasma membrane, suggesting that Slt2 inhibits TORC2 by promoting Avo2 dissociation. Our findings are the first demonstration that TORC2 function is regulated by MAPK-mediated phosphorylation.Comment: This work was supported by National Institutes of Health (NIH) Predoctoral Traineeship GM07232 and a University of California at Berkeley MacArthur and Lakhan-Pal Graduate Fellowship to K.L.L., Erwin Schroedinger Fellowship J3787-B21 from the Austrian Science Fund to AE-A, Marie Sklodowska-Curie Action H2020-MSCA-IF-2016 InsiliCardio, GA 75083 to CMA, and NIH R01 research grant GM21841 to J

Unfolding kinetics of beta-lactoglobulin induced by surfactant and denaturant: a stopped-flow/fluorescence study

The beta ->alpha transition of beta-lactoglobulin, a globular protein abundant in the milk of several mammals, is investigated in this work. This transition, induced by the cationic surfactant dodecyltrimethylammonium chloride (DTAC), is accompanied by partial unfolding of the protein. In this work, unfolding of bovine beta-lactoglobulin in DTAC is compared with its unfolding induced by the chemical denaturant guanidine hydrochloride (GnHCl). The final protein states attained in the two media have quite different secondary structure: in DTAC the alpha-helical content increases, leading to the so-called alpha-state; in GnHCl the amount of ordered secondary-structure decreases, resulting in a random coil-rich final state (denatured, or D, state). To obtain information on both mechanistic routes, in DTAC and GnHCl, and to characterize intermediates, the kinetics of unfolding were investigated in the two media. Equilibrium and kinetic data show the partial accumulation of an on-pathway intermediate in each unfolding route: in DTAC, an intermediate (I-1) with mostly native secondary structure but loose tertiary structure appears between the native (beta) and alpha-states; in GnHCl, another intermediate (I-2) appears between states beta and D. Kinetic rate constants follow a linear Chevron-plot representation in GnHCl, but show a more complex mechanism in DTAC, which acts like a stronger binding species.info:eu-repo/semantics/publishedVersio

Perceived barriers in family-based behavioural treatment of paediatric obesity – Results from the FABO study

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: To date, few studies have investigated perceived barriers among those who participate in and drop out of family-based behavioural treatment (FBT) for paediatric obesity. Examining experienced barriers during treatment, and their role in participation and completion of treatment has important implications for clinical practice. Objectives: To compare perceived barriers to participating in a family-based behavioural social facilitation treatment (FBSFT) for obesity among families who completed and did not complete treatment. Methods: Data were analysed from 90 families of children and adolescents (mean (M) age = 12.8 years, standard deviation (SD) = 3.05) with severe obesity enrolled in a 17-session FBSFT program. After completing 12 sessions or at the time of dropout, parents and therapists completed the Barriers to Treatment Participation Scale (BTPS), a 5-point Likert scale (1 = never a problem, 5 = very often a problem) which includes four subscales: 1. Stressors and obstacles that compete with treatment, 2. Treatment demands and issues, 3. Perceived relevance of treatment, 4. Relationship with the therapist. Results: Families who did not complete treatment scored significantly higher on the BTPS subscales stressors and obstacles that compete with treatment (M = 2.03, SD = 0.53 vs. M = 1.70, SD = 0.42), p = 0.010 and perceived relevance of treatment (M = 2.27, SD = 0.48 vs. M = 1.80, SD = 0.50), p < 0.001 than families who completed treatment. No other significant differences between groups were observed. Conclusion: Families are more likely to drop out of FBSFT when experiencing a high burden from life stressors or when treatment is not meeting the expectations and perceived needs of the family.publishedVersio

Family-based treatment of children with severe obesity in a public healthcare setting: Results from a randomized controlled trial

To compare the effectiveness of family-based behavioural social facilitation treatment (FBSFT) versus treatment as usual (TAU) in children with severe obesity. Parallel-design, nonblinded, randomized controlled trial conducted at a Norwegian obesity outpatient clinic. Children aged 6–18 years referred to the clinic between 2014 and 2018 were invited to participate. Participants were randomly allocated using sequentially numbered, opaqued, sealed envelopes. FBSFT (n = 59) entailed 17 sessions of structured cognitive behavioural treatment, TAU (n = 55) entailed standard lifestyle counselling sessions every third month for 1 year. Primary outcomes included changes in body mass index standard deviation score (BMI SDS) and percentage above the International Obesity Task Force cut-off for overweight (%IOTF-25). Secondary outcomes included changes in sleep, physical activity, and eating behaviour. From pre- to posttreatment there was a statistically significant difference in change in both BMI SDS (0.19 units, 95% confidence interval [CI]: 0.10–0.28, p < .001) and %IOTF-25 (5.48%, 95%CI: 2.74–8.22, p < .001) between FBSFT and TAU groups. FBSFT participants achieved significant reductions in mean BMI SDS (0.16 units, (95%CI: −0.22 to −0.10, p < .001) and %IOTF-25 (6.53%, 95% CI: −8.45 to −4.60, p < .001), whereas in TAU nonsignificant changes were observed in BMI SDS (0.03 units, 95% CI: −0.03 to 0.09, p = .30) and %IOTF-25 (−1.04%, 95% CI: −2.99 to −0.90, p = .29). More FBSFT participants (31.5%) had clinically meaningful BMI SDS reductions of ≥0.25 from pre- to posttreatment than in TAU (13.0%, p = .021). Regarding secondary outcomes, only changes in sleep timing differed significantly between groups. FBSFT improved weight-related outcomes compared to TAU.publishedVersio

Теоретико-методологічні основи розуміння механізму правового регулювання

Метою цієї статті є аналіз напрямів наукових досліджень, що у своїй єдності формують теорію механізму правового регулювання (МПР), розкриття теоретикометодологічних проблем, які мають місце при осмисленні МПР, визначення та систематизація методологічних підходів до розуміння МПР

Whole-body vibration training induces hypertrophy of the human patellar tendon

I Brage finner du siste tekst-versjon av artikkelen, og den kan inneholde ubetydelige forskjeller fra forlagets pdf-versjon. Forlagets pdf-versjon finner du på onlinelibrary.wiley.com / In Brage you'll find the final text version of the article, and it may contain insignificant differences from the journal's pdf version. The definitive version is available at onlinelibrary.wiley.comAnimal studies suggest that regular exposure to whole-body vibration (WBV) induces an anabolic response in bone and tendon. However, the effects of this type of intervention on human tendon properties and its influence on the muscle-tendon unit function have never been investigated. The aim of this study was to investigate the effect of WBV training on the patellar tendon mechanical, material and morphological properties, the quadriceps muscle architecture and the knee extension torque–angle relationship. Fifty-five subjects were randomized into either a vibration, an active control, or an inactive control group. The active control subjects performed isometric squats on a vibration platform without vibration. Muscle and tendon properties were measured using ultrasonography and dynamometry. Vibration training induced an increase in proximal (6.3%) and mean (3.8%) tendon cross-sectional area, without any appreciable change in tendon stiffness and modulus or in muscle architectural parameters. Isometric torque at a knee angle of 90° increased in active controls (6.7%) only and the torque–angle relation remained globally unchanged in all groups. The present protocol did not appreciably alter knee extension torque production or the musculo-tendinous parameters underpinning this function. Nonetheless, this study shows for the first time that WBV elicits tendon hypertrophy in humans.Seksjon for fysisk prestasjonsevne / Department of Physical Performanc

Effect of standing posture during whole body vibration training on muscle morphology and function in older adults: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Whole body vibration (WBV) is a novel modality of exercise shown to improve musculoskeletal function. This study aims to examine the effects of standing posture during low magnitude WBV training on muscle function and muscle morphology in older adults.</p> <p>Methods</p> <p>Nineteen men and women (50-80 years) were recruited to a three month randomised controlled trial and allocated to one of three groups: WBV with flexed knees (FK), WBV with locked knees (LK), or sham WBV with flexed knees (CON). Exposure was intermittent (1 min WBV:1 min rest) for 20 min, three times per week for 13 weeks. Measurements were taken at baseline and at three months. Primary outcomes included upper and lower body muscle function (strength, power and velocity). Secondary outcomes were muscle morphology, balance, habitual and maximal gait velocity, stair climb power, and chair stand performance.</p> <p>Results</p> <p>Sixteen subjects completed the study. Relative (%) upper body contraction velocity improved significantly after WBV with FK compared to LK (FK 16.0%, LK -7.6%, CON 4.7, p = 0.01). Relative upper body strength (LK 15.1%, p = 0.02; FK 12.1%, p = 0.04; CON 4.7%) increased significantly following WBV compared to control. Absolute (p = 0.05) and relative (p = 0.03) lower leg strength significantly improved with both standing postures (LK 14.4%; FK 10.7%; CON 1.3%). Only the LK group differed significantly from CON in relative leg strength gains (p = 0.02). Potentially clinically meaningful but statistically non-significant improvements in lower leg muscle cross-sectional area (LK 3.7 cm², FK 2.4 cm², CON 2.2 cm²p = 0.13) were observed after WBV with LK compared to the other groups. No significant effects of WBV on any functional performance tests were observed.</p> <p>Conclusions</p> <p>Our results suggest that WBV may improve muscle strength and contraction velocity in some muscle groups in older adults. However, hypothesised differential adaptation to standing posture (FK > LK) was observed only for upper body contraction velocity, making recommendations regarding this prescriptive element inconclusive. The efficacy, mechanism of action and long term feasibility of WBV for musculoskeletal health in older adults warrants continued investigation in robustly designed, sufficiently powered future studies.</p> <p>Trial Registration</p> <p>ACTRN12609000353291.</p

The Saudi experiment with career guidance

Saudi Arabia has recently embarked on an ambitious experiment with career guidance. The country has identified that career guidance offers a range of potential cultural, educational and economic benefits. These include supporting the Saudisation of the workforce, the development of the vocational education system and the engagement of the Saudi ‘youth bulge’ in the labour market and wider society. However, the country has a weak tradition of career guidance and a need to develop new policies and systems rapidly. The Saudi Ministry of Labour has driven the development of the country’s new career guidance system and has sought to learn from global best practice. However, Saudi Arabia offers a very different context from those where career guidance has flourished. Particularly distinctive features of Saudi society include its limited civil society, the central role that religion plays, the place of women, the role of oil within the economy and the high level of migrant workers in the labour market. Taken together these issues offer challenges of culture, theory, policy and practice. Negotiating these challenges and building an organic body of theory and practice will be critical to the success or otherwise of the Saudi experiment with career guidance.N/

Low-frequency vibratory exercise reduces the risk of bone fracture more than walking: a randomized controlled trial

BACKGROUND: Whole-body vibration (WBV) is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people. There are two currently marketed vibrating plates: a) the whole plate oscillates up and down; b) reciprocating vertical displacements on the left and right side of a fulcrum, increasing the lateral accelerations. A few studies have shown recently the effectiveness of the up-and-down plate for increasing Bone Mineral Density (BMD) and balance; but the effectiveness of the reciprocating plate technique remains mainly unknown. The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women. METHODS: Twenty-eight physically untrained post-menopausal women were assigned at random to a WBV group or a Walking group. Both experimental programmes consisted of 3 sessions per week for 8 months. Each vibratory session included 6 bouts of 1 min (12.6 Hz in frequency and 3 cm in amplitude with 60° of knee flexion) with 1 min rest between bouts. Each walking session was 55 minutes of walking and 5 minutes of stretching. Hip and lumbar BMD (g·cm(-2)) were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test. ANOVA for repeated measurements was adjusted by baseline data, weight and age. RESULTS: After 8 months, BMD at the femoral neck in the WBV group was increased by 4.3% (P = 0.011) compared to the Walking group. In contrast, the BMD at the lumbar spine was unaltered in both groups. Balance was improved in the WBV group (29%) but not in the Walking group. CONCLUSION: The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures: hip BMD and balance