Internalization of novel non-viral vector TAT-streptavidin into human cells

BACKGROUND: The cell-penetrating peptide derived from the Human immunodeficiency virus-1 transactivator protein Tat possesses the capacity to promote the effective uptake of various cargo molecules across the plasma membrane in vitro and in vivo. The objective of this study was to characterize the uptake and delivery mechanisms of a novel streptavidin fusion construct, TAT(47–57)-streptavidin (TAT-SA, 60 kD). SA represents a potentially useful TAT-fusion partner due to its ability to perform as a versatile intracellular delivery vector for a wide array of biotinylated molecules or cargoes. RESULTS: By confocal and immunoelectron microscopy the majority of internalized TAT-SA was shown to accumulate in perinuclear vesicles in both cancer and non-cancer cell lines. The uptake studies in living cells with various fluorescent endocytic markers and inhibiting agents suggested that TAT-SA is internalized into cells efficiently, using both clathrin-mediated endocytosis and lipid-raft-mediated macropinocytosis. When endosomal release of TAT-SA was enhanced through the incorporation of a biotinylated, pH-responsive polymer poly(propylacrylic acid) (PPAA), nuclear localization of TAT-SA and TAT-SA bound to biotin was markedly improved. Additionally, no significant cytotoxicity was detected in the TAT-SA constructs. CONCLUSION: This study demonstrates that TAT-SA-PPAA is a potential non-viral vector to be utilized in protein therapeutics to deliver biotinylated molecules both into cytoplasm and nucleus of human cells

Does the company's economic performance affect access to occupational health services?

<p>Abstract</p> <p>Background</p> <p>In Finland like in many other countries, employers are legally obliged to organize occupational health services (OHS) for their employees. Because employers bear the costs of OHS it could be that in spite of the legal requirement OHS expenditure is more determined by economic performance of the company than by law. Therefore, we explored whether economic performance was associated with the companies' expenditure on occupational health services.</p> <p>Methods</p> <p>We used a prospective design to predict expenditure on OHS in 2001 by a company's economic performance in 1999. Data were provided by Statistics Finland and expressed by key indicators for profitability, solidity and liquidity and by the Social Insurance Institution as employers' reimbursement applications for OHS costs. The data could be linked at the company level. Regression analysis was used to study associations adjusted for various confounders.</p> <p>Results</p> <p>Nineteen percent of the companies (N = 6 155) did not apply for reimbursement of OHS costs in 2001. The profitability of the company represented by operating margin in 1999 and adjusted for type of industry was not significantly related to the company's probability to apply for reimbursement of the costs in 2001 (OR = 1.00, 95%CI: 0.99 to 1.01). Profitability measured as operating profit in 1999 and adjusted for type of industry was not significantly related to costs for curative medical services (Beta -0.001, 95%CI: -0.00 to 0.11) nor to OHS cost of prevention in 2001 (Beta -0.001, 95%CI: -0.00 to 0.00).</p> <p>Conclusion</p> <p>We did not find a relation between the company's economic performance and expenditure on OHS in Finland. We suppose that this is due to legislation obliging employers to provide OHS and the reimbursement system both being strong incentives for employers.</p

Maahanmuuttaja osalliseksi ja työhön : Policy Brief

Non peer reviewe

Fatigue-induced changes of impedance and performance in target tracking

Kinematic variability is caused, in part, by force fluctuations. It has been shown empirically and numerically that the effects of force fluctuations on kinematics can be suppressed by increasing joint impedance. Given that force variability increases with muscular fatigue, we hypothesized that joint impedance would increase with fatigue to retain a prescribed accuracy level. To test this hypothesis, subjects tracked a target by elbow flexion and extension both with fatigued and unfatigued elbow flexor and extensor muscles. Joint impedance was estimated from controlled perturbations to the elbow. Contrary to the hypothesis, elbow impedance decreased, whereas performance, expressed as the time-on-target, was unaffected by fatigue. Further analysis of the data revealed that subjects changed their control strategy with increasing fatigue. Although their overall kinematic variability increased, task performance was retained by staying closer to the center of the target when fatigued. In conclusion, the present study reveals a limitation of impedance modulation in the control of movement variability

Preventing stroke in people with atrial fibrillation: a cross-sectional study.

The annual stroke rate in atrial fibrillation is around 5 per cent with increased risk in those with hypertension, diabetes, left ventricular dysfunction and other cardiovascular risk factors. This study set out to identify the patients with atrial fibrillation and modifiable risk factors for stroke

Structure of the Odd-A, Shell-stabilized nucleus No102253

In-beam γ-ray spectroscopic measurements have been made on No102253. A single rotational band was identified up to a probable spin of 39/2, which is assigned to the 7/2+[624] Nilsson configuration. The bandhead energy and the moment of inertia provide discriminating tests of contemporary models of the heaviest nuclei. Novel methods were required to interprete the sparse data set associated with cross sections of around 50nb. These methods included comparisons of experimental and simulated spectra, as well as testing for evidence of a rotational band in the γγ matrix

Identification of yrast states in 187Pb

g -ray spectroscopy of the high-spin states of the neutron-deficient nucleus 187Pb has been conducted with the 155Gd(36Ar,4n) reaction. A cascade of three transitions was deduced from g -g coincidence data gated by detection of recoiling evaporation residues in a gas-filled recoil separator. In an earlier, separate experiment, two of these g rays were positively identified with 187Pb by recoil-g coincidence measurements with a high-resolution, recoil mass spectrometer. From comparison with similar sequences in heavier odd-A lead isotopes, the cascade in 187Pb is associated with the sequence of three E2 transitions from the yrast 25/2 + level to a low-lying 13/2 + isomer. The variation of excitation energy with mass number of the levels concerned suggests that their structure can be associated with weak coupling of an odd i13/2 neutron to states in the spherical well. However, the possibility that they are influenced by mixing with states in the prolate-deformed well cannot be discounted

The clinical course of low back pain: a meta-analysis comparing outcomes in randomised clinical trials (RCTs) and observational studies.

BACKGROUND: Evidence suggests that the course of low back pain (LBP) symptoms in randomised clinical trials (RCTs) follows a pattern of large improvement regardless of the type of treatment. A similar pattern was independently observed in observational studies. However, there is an assumption that the clinical course of symptoms is particularly influenced in RCTs by mere participation in the trials. To test this assumption, the aim of our study was to compare the course of LBP in RCTs and observational studies. METHODS: Source of studies CENTRAL database for RCTs and MEDLINE, CINAHL, EMBASE and hand search of systematic reviews for cohort studies. Studies include individuals aged 18 or over, and concern non-specific LBP. Trials had to concern primary care treatments. Data were extracted on pain intensity. Meta-regression analysis was used to compare the pooled within-group change in pain in RCTs with that in cohort studies calculated as the standardised mean change (SMC). RESULTS: 70 RCTs and 19 cohort studies were included, out of 1134 and 653 identified respectively. LBP symptoms followed a similar course in RCTs and cohort studies: a rapid improvement in the first 6 weeks followed by a smaller further improvement until 52 weeks. There was no statistically significant difference in pooled SMC between RCTs and cohort studies at any time point:- 6 weeks: RCTs: SMC 1.0 (95% CI 0.9 to 1.0) and cohorts 1.2 (0.7to 1.7); 13 weeks: RCTs 1.2 (1.1 to 1.3) and cohorts 1.0 (0.8 to 1.3); 27 weeks: RCTs 1.1 (1.0 to 1.2) and cohorts 1.2 (0.8 to 1.7); 52 weeks: RCTs 0.9 (0.8 to 1.0) and cohorts 1.1 (0.8 to 1.6). CONCLUSIONS: The clinical course of LBP symptoms followed a pattern that was similar in RCTs and cohort observational studies. In addition to a shared 'natural history', enrolment of LBP patients in clinical studies is likely to provoke responses that reflect the nonspecific effects of seeking and receiving care, independent of the study design