Ser649 and Ser650 Are the Major Determinants of Protein Kinase A-Mediated Activation of Human Hormone-Sensitive Lipase against Lipid Substrates

BACKGROUND: Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from stored triacylglycerols. Its activity is regulated by reversible protein phosphorylation. In rat HSL Ser563, Ser659 and Ser660 have been shown to be phosphorylated by protein kinase A (PKA) in vitro as well as in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In this study we employed site-directed mutagenesis, in vitro phosphorylation and mass spectrometry to show that in vitro phosphorylation of human HSL by PKA occurs primarily on Ser649 and Ser650 (Ser659 and Ser660 in rat HSL). The wild type enzyme and four mutants were expressed in C-terminally His-tagged form in Sf9 insect cells and purified to homogeneity. HSL variants in which Ser552 and/or Ser554 were mutated to Ala or Glu retained both lipolytic and non-lipolytic activity and were phosphorylated by PKA and activated to a similar extent as the wild type enzyme. (32)P-labeling studies revealed that the bulk of the phosphorylation was on the Ser649/Ser650 site, with only a minor phosphorylation of Ser552 and Ser554. MS/MS analysis demonstrated that the peptide containing Ser649 and Ser650 was primarily phosphorylated on Ser650. The mutant lacking all four serines had severely reduced lipolytic activity, but a lesser reduction in non-lipolytic activity, had S(0.5) values for p-nitrophenol butyrate and triolein comparable to those of wild type HSL and was not phosphorylated by PKA. PKA phosphorylation of the wild type enzyme resulted in an increase in both the maximum turnover and S(0,5) using the TO substrate. CONCLUSIONS: Our results demonstrate that PKA activates human HSL against lipid substrates in vitro primarily through phosphorylation of Ser649 and Ser650. In addition the results suggest that Ser649 and Ser650 are located in the vicinity of a lipid binding region and that PKA phosphorylation controls the accessibility of this region

Potential unique causes of burnout for chiropractic professionals

Objective The objective of this narrative review is to discuss the potential for burnout in chiropractic practitioners. This discussion is grounded in the job demands-resource model, the conservation of resources model, the unique profession-specific stressors experienced by chiropractors, and information from similar health care professions. Methods A search using both the indexed (PubMed and PsychLit) and nonindexed psychosocial literature was used. Other resources included the Cochrane Library, articles from governing bodies of the chiropractic profession, trade magazines, and research conferences and symposium proceedings. Articles were analyzed following the grounded theory principles: open coding and memos for conceptual labeling, axial coding and memos for category building, and selective coding for model building. Results Potential stressors unique to doctors of chiropractic include factors associated with physical workload, role stress, and mental and emotional demands. Conclusions There are unique chiropractic-specific occupational characteristics that possibly contribute to burnout in the chiropractic professionals. These findings emphasize the need for assessing and measuring burnout and attrition within the chiropractic profession

The impact of televised tobacco control advertising content on campaign recall: evidence from the International Tobacco Control (ITC) United Kingdom Survey

BACKGROUND: Although there is some evidence to support an association between exposure to televised tobacco control campaigns and recall among youth, little research has been conducted among adults. In addition, no previous work has directly compared the impact of different types of emotive campaign content. The present study examined the impact of increased exposure to tobacco control advertising with different types of emotive content on rates and durations of self-reported recall. METHODS: Data on recall of televised campaigns from 1,968 adult smokers residing in England through four waves of the International Tobacco Control (ITC) United Kingdom Survey from 2005 to 2009 were merged with estimates of per capita exposure to government-run televised tobacco control advertising (measured in GRPs, or Gross Rating Points), which were categorised as either “positive” or “negative” according to their emotional content. RESULTS: Increased overall campaign exposure was found to significantly increase probability of recall. For every additional 1,000 GRPs of per capita exposure to negative emotive campaigns in the six months prior to survey, there was a 41% increase in likelihood of recall (OR = 1.41, 95% CI: 1.24–1.61), while positive campaigns had no significant effect. Increased exposure to negative campaigns in both the 1–3 months and 4–6 month periods before survey was positively associated with recall. CONCLUSIONS: Increased per capita exposure to negative emotive campaigns had a greater effect on campaign recall than positive campaigns, and was positively associated with increased recall even when the exposure had occurred more than three months previously

Emergence of contact injuries in invasion team sports : an ecological dynamics rationale

The incidence of contact injuries in team sports is considerable, and injury mechanisms need to be comprehensively understood to facilitate the adoption of preventive measures. In Association Football, evidence shows that the highest prevalence of contact injuries emerges in one-on-one interactions. However, previous studies have tended to operationally report injury mechanisms in isolation, failing to provide a theoretical rationale to explain how injuries might emerge from interactions between opposing players. In this position paper, we propose an ecological dynamics framework to enhance current understanding of behavioural processes leading to contact injuries in team sports. Based on previous research highlighting the dynamics of performer–environment interactions, contact injuries are proposed to emerge from symmetry-breaking processes during on-field interpersonal interactions among competing players and the ball. Central to this approach is consideration of candidate control parameters that may provide insights on the information sources used by players to reduce risk of contact injuries during performance. Clinically, an ecological dynamics analysis could allow sport practitioners to design training sessions based on selected parameter threshold values as primary and/or secondary preventing measures during training and rehabilitation sessions

Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment

\ua9 The Author(s) 2024. The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer’s Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer’s Disease-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aβ. Hydrodynamic calculations suggest Aβ aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis

Sn-Beta zeolites with borate salts catalyse the epimerization of carbohydrates via an intramolecular carbon shift

Carbohydrate epimerization is an essential technology for the widespread production of rare sugars. In contrast to other enzymes, most epimerases are only active on sugars substituted with phosphate or nucleotide groups, thus drastically restricting their use. Here we show that Sn-Beta zeolite in the presence of sodium tetraborate catalyses the selective epimerization of aldoses in aqueous media. Specifically, a 5 wt% aldose (for example, glucose, xylose or arabinose) solution with a 4:1 aldose:sodium tetraborate molar ratio reacted with catalytic amounts of Sn-Beta yields near-equilibrium epimerization product distributions. The reaction proceeds by way of a 1,2 carbon shift wherein the bond between C-2 and C-3 is cleaved and a new bond between C-1 and C-3 is formed, with C-1 moving to the C-2 position with an inverted configuration. This work provides a general method of performing carbohydrate epimerizations that surmounts the main disadvantages of current enzymatic and inorganic processes.National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Award DMR-0819762)DuPont MIT Alliance (Graduate Research Fellowship)National Institutes of Health (U.S.) (Grant EB-001960)National Institutes of Health (U.S.) (Grant EB-002026)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374

Knee kinematics and kinetics in former soccer players with a 16-year-old ACL injury – the effects of twelve weeks of knee-specific training

BACKGROUND: Training of neuromuscular control has become increasingly important and plays a major role in rehabilitation of subjects with an injury to the anterior cruciate ligament (ACL). Little is known, however, of the influence of this training on knee stiffness during loading. Increased knee stiffness occurs as a loading strategy of ACL-injured subjects and is associated with increased joint contact forces. Increased or altered joint loads contribute to the development of osteoarthritis. The aim of the study was to determine if knee stiffness, defined by changes in knee kinetics and kinematics of gait, step activity and cross-over hop could be reduced through a knee-specific 12-week training programme. METHODS: A 3-dimensional motion analysis system (VICON) and a force plate (AMTI) were used to calculate knee kinetics and kinematics before and after 12 weeks of knee-specific training in 12 males recruited from a cohort with ACL injury 16 years earlier. Twelve uninjured males matched for age, sex, BMI and activity level served as a reference group. Self-reported patient-relevant data were obtained by the KOOS questionnaire. RESULTS: There were no significant changes in knee stiffness during gait and step activity after training. For the cross-over hop, increased peak knee flexion during landing (from 44 to 48 degrees, p = 0.031) and increased internal knee extensor moment (1.28 to 1.55 Nm/kg, p = 0.017) were seen after training, indicating reduced knee stiffness. The KOOS sport and recreation score improved from 70 to 77 (p = 0.005) and was significantly correlated with the changes in knee flexion during landing for the cross-over hop (r = 0.6, p = 0.039). CONCLUSION: Knee-specific training improved lower extremity kinetics and kinematics, indicating reduced knee stiffness during demanding hop activity. Self-reported sport and recreational function correlated positively with the biomechanical changes supporting a clinical importance of the findings. Further studies are needed to confirm these results in women and in other ACL injured populations

Health care seeking among pulmonary tuberculosis suspects and patients in rural Ethiopia: a community-based study

<p>Abstract</p> <p>Background</p> <p>Health care seeking is a dynamic process that is influenced by socio-demographic, cultural and other factors. In Ethiopia, there are limited studies regarding the health seeking behaviour of tuberculosis (TB) suspects and TB patients. However, a thorough understanding of patients' motivation and actions is crucial to understanding TB and the treatment of disease. Such insights would conceivably help to reduce delay in diagnosis, improve treatment adherence and thereby reduce transmission of TB in the community. The objective of this study was to describe and analyze health care seeking among TB suspects and pulmonary TB (PTB) cases in a rural district of the Amhara Region in Ethiopia.</p> <p>Methods</p> <p>Study <it>kebeles </it>were randomly selected in a cross-sectional study design. House-to-house visits were conducted in which individuals aged 15 years and above in all households of the <it>kebeles </it>were included. Subjects with symptoms suggestive of TB were interviewed about their health seeking behaviour, socio-demographic and clinical factors using a semi-structured questionnaire. Logistics regression analysis was employed to assess associations between the independent and outcome variables.</p> <p>Results</p> <p>The majority, 787 (78%), TB suspects and 33 (82.5%) PTB cases had taken health care actions for symptoms from sources outside their homes. The median delay before the first action was 30 days. In logistics regression, women (AOR 0.8, 95% CI 0.6, 0.9) were found to be less likely to visit a medical health provider than men. Those with a long duration of cough (AOR 1.5, 95% CI 1.03, 2.1) and those with a previous history of TB (AOR 1.5, 95% CI 1.03, 2.3) were more likely to visit a medical health provider compared to those with a shorter duration of cough and with no history of TB.</p> <p>Conclusion</p> <p>The majority of TB suspects and PTB cases had already taken health care actions for their symptoms at the time of the survey. The availability of a simple and rapid diagnostic TB test for use at the lowest level of health care and the involvement of all health providers in case finding activities are imperative for early TB case detection.</p

Characteristics of Suicide Attempts in Anorexia and Bulimia Nervosa: A Case–Control Study

Objective: Compared to other eating disorders, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an eating disorders (ED). Method: Case-control study in a cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity. Results: AN patients were more likely to have made a serious attempt (OR = 3.4, 95 % CI 1.4–7.9), with a higher expectation of dying (OR = 3.7,95 % CI 1.1–13.5), and an increased risk of severity (OR = 3.4,95 % CI 1.2–9.6). BN patients did not differ from the control group. Clinical markers of the severity of ED were associated with the seriousness of the attempt. Conclusion: There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Higher completed suicide rates in AN may be partially explained by AN patients ’ higher desire to die and their more severe and lethal attempts