Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.     

The intraocular staining potential of anthocyanins and their retinal biocompatibility: a preclinical study

Purpose: To perform preclinical studies to determine the efficacy and safety of anthocyanins as stains for the internal limiting membrane (ILM) of the eye.

Materials and methods: Cyanidin (Cya), delphinidin (Del), luteolinidin (Lut), peonidin (Peo) and pelargonidin (Pel) were evaluated. These natural dyes were used to stain the lens capsule and ILM of pig eyes. The effects of these dyes on retinal cell viability was determined using a water-soluble tetrazolium salt assay, and oxidative stress was measured in vitro. Histopathology, in situ TUNEL labelling, transmission electronic microscopy (TEM), and electroretinography (ERG) were performed on rats following the intravitreal and subretinal injection of the neuroprotective dyes.

Results: All anthocyanins stained the lens capsule and ILM of the pigs at a concentration of 1?mg/ml. Del, Lut and Peo were non-toxic and produced survival rates in the ARPE19 and RGC5 cells that were similar to those in control cells. We treated eyes with H₂O₂ and three dyes (Del, Lut, and Peo) to explore the possible neuroprotective effects and observed significantly higher survival rates in the ARPE19 cells treated with Del, Lut or Peo and the RGC5 cells treated with Lut or Peo than those in the control cells. Three dyes were intravitreally and subretinally injected into rats in vivo, and the histology showed mildly disorganized retinal cell layers. TUNEL staining and TEM examinations did not reveal additional toxic effects. Rat ERGs were not altered after intravitreal injections.

Conclusions: This preclinical study, Del, Lut, and Peo show potential as staining agents and warrant further investigation as vital dyes.     

Maternal Multivitamin Intake,Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring

Background

To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B₁₂ levels at birth and child's Autism Spectrum Disorder (ASD) risk.

Methods

This report included 1257 mother–child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B₁₂ were measured from samples taken 2–3 days after birth.

Results

Moderate (3–5 times/week) self‐reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B₁₂ (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5).

Conclusion

There was a ‘U shaped’ relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B₁₂ levels at birth were associated with ASD risk. This hypothesis‐generating study does not question the importance of consuming adequate folic acid and vitamin B₁₂ during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B₁₂ exposure in‐utero on early brain development.     

Agreeableness and pregnancy: Relations with coping and psychiatric symptoms,a longitudinal study on Spanish pregnant women

ABSTRACT

Agreeableness is associated with good mental health during pregnancy. Although different studies have indicated that agreeableness is related to adaptive coping, this relation has scarcely been studied in pregnant women. The aim of this study was to analyze the possible differences between high and low agreeableness in relation to coping strategies and psychiatric symptoms in pregnant women. We conducted a longitudinal prospective study between October 2009 and January 2013. Pregnant women (n = 285) were assessed in the first trimester of pregnancy, and 122 of them were assessed during the third. Data were collected using the Coping Strategies Questionnaire, the Symptom Check List 90-R, and the agreeableness subscale of the NEO-FFI. Using the SPSS 21 statistics package, binary logistic regression, two-way mixed analysis of variance, and multiple regression analyses and a Sobel test were conducted. Higher levels of agreeableness were associated with positive reappraisal and problem-solving, and lower levels of agreeableness were associated with overt emotional expression and negative self-focused coping. Women with low agreeableness had poorer mental health, especially in the first trimester. These findings should be taken into account to improve women’s experiences during pregnancy. Nevertheless, given the scarcity of data, additional studies are needed.     

The intersection of identities in supervision for trauma-informed practice: Challenges and strategies

ABSTRACT

This article discusses and illustrates the role and impact of the intersection of supervisors’ and supervisees’ social identities and the associated power and privilege within the context of supervision for trauma-informed practice. Based on current theoretical, empirical, and practice literature, challenges related to the supervisor’s and supervisee’s racial, ethnicity, gender, social class, and additional social affiliations are identified, as are strategies for addressing them within supervision for trauma-informed practice. A case example drawn from the authors’ experiences illustrates the importance of attending to intersectionality in trauma-informed supervision Suggestions for future research efforts are offered.     

Investigating self-reported health by occupational group after a 10-year lag: results from the total Belgian workforce

Background

Belgium lacks a systematic overview of health differences by occupation. This is the first study to examine self-reported health among 27 occupational groups in Belgium with a lag time of 10 years.

Methods

Individual data are derived from an anonymous linkage between the 1991 and 2001 Belgian census. The total working population (25–55 years) is selected from the 1991 Belgian census. Self-reported health (1?=?fair or (very) bad health; 0?=?(very) good health) was obtained from the 2001 census. Logistic regression analysis was used to analyse the health of 1.5 million men and 1.0 million women by occupational group in 1991. The active sex-specific population in 1991 and 2001 was the reference group. Controls include age, activity status and housing status at the time of 2001 census.

Results

Both male and female workers in physically demanding occupations were more likely to report poor health. The three occupations with the highest age-adjusted Odds Ratios (OR) were extraction and building trade workers (OR_male 2.08 95% Confidence Interval (CI) 2.05–2.10; OR_female 2.15 CI 1.93–2.40); services elementary workers (OR_male 2.06 CI 2.03–2.10; OR_female 2.37 CI 2.34–2.41); and labourers in construction, manufacturing and transport (OR_male 1.90 CI 1.86–1.93; OR_female 2.21 CI 2.12–2.29). Men and women in teaching, scientific, health-related and managerial positions had the lowest age-adjusted ORs for poor self-reported health. The pattern in occupational health differences remained the same after controlling for activity status and socio-economic position.

Conclusions

Occupational health inequalities are apparent after a lag time of 10 years. The identification of types of workers in poor health provide valuable insights to future health promotion strategies in the Belgian workforce.