The HIV-1 nucleocapsid (NC) protein is a small, basic protein containing two retroviral zinc fingers. It is a highly active nucleic acid chaperone; because of this activity, it plays a crucial role in virus replication as a cofactor during reverse transcription, and is probably important in other steps of the replication cycle as well. We previously reported that NC binds with high-affinity to the repeating sequence d(TG)n. We have now analyzed the interaction between NC and d(TG)4 in considerable detail, using surface plasmon resonance (SPR), tryptophan fluorescence quenching (TFQ), fluorescence anisotropy (FA), isothermal titration calorimetry (ITC) and electrospray ionization Fourier transform mass spectrometry (ESI-FTMS). Our results show that the interactions between these two molecules are surprisngly complex: while the Kd for binding of a single d(TG)4 molecule to NC is only ∼5 nM in 150 mM NaCl, a single NC molecule is capable of interacting with more than one d(TG)4 molecule, and conversely, more than one NC molecule can bind to a single d(TG)4 molecule. The strengths of these additional binding reactions are quantitated. The implications of this multivalency for the functions of NC in virus replication are discussed.
26This study investigated the effects of continuous moderate-intensity exercise (MIE) and high-27 intensity interval exercise (HIIE) in combination with short exposure to hypoxia on appetite and 28 plasma concentrations of acylated ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). 29Twelve healthy males completed four, 2.6 h trials in a random order: 1) MIE-normoxia, 2) MIE-30 hypoxia, 3) HIIE-normoxia, and 4) HIIE-hypoxia. Exercise took place in an environmental chamber. 31During MIE, participants ran for 50 min at 70% of altitude-specific maximal oxygen uptake (
Data Availability Statement All data generated or analysed for this review are included in this published article and its Electronic Supplementary Material documents.
Background: BMI is often used to evaluate the effectiveness of childhood obesity interventions, but such interventions may have additional benefits independent of effects on adiposity. We investigated whether benefits to health outcomes following the Mind, Exercise, Nutrition.Do It! (MEND) childhood obesity intervention were independent of or associated with changes in zBMI.Methods: A total of 79 obese children were measured at baseline; 71 and 42 participants were followed-up at 6 and 12 months respectively, and split into four groups depending on magnitude of change in zBMI. Differences between groups for waist circumference, cardiovascular fitness, physical and sedentary activities, and self-esteem were investigated.Results: Apart from waist circumference and its z-score, there were no differences or trends across zBMI subgroups for any outcome. Independent of the degree of zBMI change, benefits in several parameters were observed in children participating in this obesity intervention.Conclusion: We concluded that isolating a single parameter like zBMI change and neglecting other important outcomes is restrictive and may undermine the evaluation of childhood obesity intervention effectiveness.
Background: In the current study we report outcomes 2.4 years from baseline
This study evaluated the acute effects of interrupting prolonged sitting with an accumulated 2 h of light-intensity walking on postprandial cardiometabolic risk markers. In this randomised crossover trial, 24 participants (twelve males) aged 18-55 years took part in two, 6.5 h conditions: 1) prolonged sitting (SIT) and 2) sitting interrupted hourly with 20 min light-intensity treadmill desk walking at between 1.2-3.5 km/h (INT-SIT). Standardized meals were provided at 0 h and 3 h. Blood samples and blood pressure measures were taken hourly. Statistical analyses were completed using linear mixed models. Postprandial incremental area under the curve responses (mmol/L∙6.5 h) for glucose (4.52 [3.47, 5.56] and 6.66 [5.62, 7.71] for INT-SIT and SIT, respectively) and triglycerides (1.96 [0.96, 2.96] and 2.71 [1.70, 3.71] for INT-SIT and SIT, respectively) were significantly lower in INT-SIT than SIT. Mean systolic and diastolic blood pressure responses were lower by 3% and 4%, respectively, in INT-SIT than SIT (P < 0.05). There was no significant condition x sex interaction effect for any outcomes (P > 0.05). These findings suggest that interrupting sitting with an accumulated 2 h of light-intensity walking acutely improves cardiometabolic risk levels in males and females compared with prolonged sitting.
Children’s engagement in physical activity of a vigorous intensity or higher is more effective at promoting cardiorespiratory fitness than moderate physical activity. It remains unclear how higher intensity physical activity varies between days when schoolchildren participate in physical education (PE) and non-PE days. The purpose of this study was to assess how PE contributes to sedentary behaviour and the intensity profile of physical activity accumulated on PE days compared to non-PE days. Fifty-three schoolchildren (36 girls, 11.7 ± 0.3 years) completed five-day minute-by-minute habitual physical activity monitoring using triaxial accelerometers to determine time spent sedentary (<1.5 Metabolic Equivalent of Tasks (METs)) and in light (1.5–2.9 METs), moderate (3–5.9 METs), vigorous (6–8.9 METs), hard (9–11.9 METs) and very hard intensity (≥12 METs) physical activity on PE days and non-PE days. Sedentary time was higher on non-PE days than on PE days (mean difference: 62 minutes, p < 0.001). Hard and very hard intensity physical activity was significantly higher on PE days compared with non-PE days (mean total difference: 33 minutes, all significant at p < 0.001). During the PE lesson, boys spent more time in hard ( p < 0.01) and very hard ( p < 0.01) physical activity compared to girls. Schoolchildren spent significantly more time in higher intensity physical activity and significantly less time sedentary on PE days than on non-PE days. As well as reducing sedentary behaviour, the opportunity to promote such health-promoting higher intensity physical activity in the school setting warrants further investigation.
BACKGROUND Preliminary data suggest that Coronavirus Disease-2019 (COVID-19) is associated with hypercoagulability and neurovascular events, but data on outcomes is limited. OBJECTIVE To report the clinical course and outcomes of a case series of COVID-19 patients with a variety of cerebrovascular events. METHODS We performed a multicentric, retrospective chart review at our three academic tertiary care hospitals, and identified all COVID-19 patients with cerebrovascular events requiring neuro-intensive care and/or neurosurgical consultation. RESULTS We identified 26 patients between March 1 and May 24, 2020, of whom 12 (46%) died. The most common event was a large-vessel occlusion (LVO) in 15 patients (58%), among whom 8 died (8/15, 53%). A total of 9 LVO patients underwent mechanical thrombectomy, of whom 5 died (5/9, 56%). A total of 7 patients (27%) presented with intracranial hemorrhage. Of the remaining patients, 2 had small-vessel occlusions, 1 had cerebral venous sinus thrombosis, and another had a vertebral artery dissection. Acute Respiratory Distress Syndrome occurred in 8 patients, of whom 7 died. Mortalities had a higher D-dimer on admission (mean 20 963 ng/mL) than survivors (mean 3172 ng/mL). Admission Glasgow Coma Scale (GCS) score was poor among mortalities (median 7), whereas survivors had a favorable GCS at presentation (median 14) and at discharge (median 14). CONCLUSION COVID-19 may be associated with hemorrhage as well as ischemia, and prognosis appears poorer than expected—particularly among LVO cases, where outcome remained poor despite mechanical thrombectomy. However, a favorable neurological condition on admission and lower D-dimer may indicate a better outcome.
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