Influence of RNA structural stability on the RNA chaperone activity of the Escherichia coli protein StpA

Proteins with RNA chaperone activity are able to promote folding of RNA molecules by loosening their structure. This RNA unfolding activity is beneficial when resolving misfolded RNA conformations, but could be detrimental to RNAs with low thermodynamic stability. In order to test this idea, we constructed various RNAs with different structural stabilities derived from the thymidylate synthase (td) group I intron and measured the effect of StpA, an Escherichia coli protein with RNA chaperone activity, on their splicing activity in vivo and in vitro. While StpA promotes splicing of the wild-type td intron and of mutants with wild-type-like stability, splicing of mutants with a lower structural stability is reduced in the presence of StpA. In contrast, splicing of an intron mutant, which is not destabilized but which displays a reduced population of correctly folded RNAs, is promoted by StpA. The sensitivity of an RNA towards StpA correlates with its structural stability. By lowering the temperature to 25°C, a temperature at which the structure of these mutants becomes more stable, StpA is again able to stimulate splicing. These observations clearly suggest that the structural stability of an RNA determines whether the RNA chaperone activity of StpA is beneficial to folding

Dry Eye Parameters and Lid Geometry in Adults Born Extremely, Very, and Moderately Preterm with and without ROP: Results from the Gutenberg Prematurity Eye Study

Background/Aims: This study aimed to analyze the effects of perinatal history on tear film properties and lid geometry in adults born preterm. Methods: The Gutenberg Prematurity Eye Study (GPES) is a German prospective examination of adults born preterm and term aged 18 to 52 years with Keratograph® 5M and Schirmer test I. Main outcome measures were first non-invasive tear film break-up time (F-NITBUT), bulbar redness (BR), Schirmer test, and nasal palpebral angle measurement. The associations with gestational age (GA), birth weight (BW), and BW percentile, retinopathy of prematurity (ROP), ROP treatment, and other perinatal factors were evaluated using regression analyses. Results: 489 eyes of 255 preterm and 277 eyes of 139 full-term individuals (aged 28.6 +/− 8.8 years, 220 females) were included. Of these, 33 participants (56 eyes) had a history of spontaneously regressed ROP and 9 participants (16 eyes) had a history of ROP treatment. After adjustment for age and sex, lower F-NITBUT (<20 s) was associated with ROP treatment (OR = 4.42; p = 0.025). Lower GA correlated with increased bulbar redness (B = −0.02; p = 0.011) and increased length of wetting in the Schirmer test (B = −0.69; p = 0.003). Furthermore, low GA was associated with narrowing of the nasal palpebral angle (B = 0.22; p = 0.011) adjusted for age and sex, but not when considering ROP in the multivariable model. Conclusion: Our analyses indicate that perinatal history affects ocular surface properties, tear production and lid geometry in adults born term and preterm. This might indicate that affected persons have a predisposition to diseases of the corneal surface such as the dry eye disease

Corneal Aberrations and Thickness in Adults Born Small, Appropriate, or Large for Gestational Age at Term

Background/Aims: This study investigated whether there are changes in corneal surface regularity and corneal thickness in adults born small, appropriate, or large for gestational age at term. Methods: This retrospective cohort study involved prospective Scheimpflug imaging of the cornea (Pentacam®) to compare the corneal thickness and aberrations between adults classified as small for gestational age (SGA), normal birth weight (BW), and large for gestational age (LGA). Multivariable linear regression was applied to analyze associations with gestational age, BW percentile, placental insufficiency, preeclampsia, and breastfeeding. Results: In total, 448 eyes of 261 individuals born full term (aged 29.9 ± 9.5 years, 140 females) were examined, including 29 severe SGA (BW 90th and 97th percentile), and 33 severe LGA (BW > 97th percentile). There were no differences between groups in the corneal aberrations of the total cornea as well as of the corneal front surface, except for higher-order aberrations in the front of the cornea (p = 0.032). There was an association between the increased total root mean square of higher-order aberrations and lower birth weight percentile (p = 0.004), with increased higher-order aberrations correlating with lower visual acuity and spherical equivalent. Conclusion: Restricted prenatal growth is associated with increased higher-order aberrations in adulthood

Anterior Chamber Angle in Adults Born Extremely, Very, and Moderately Preterm with and without Retinopathy of Prematurity&mdash;Results of the Gutenberg Prematurity Eye Study

Purpose: To determine whether prematurity and associated factors affect the anterior chamber angle (ACA) width in adulthood. Methods: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination of adults (age 18&ndash;52 years) in Germany. All participants were examined with Scheimpflug imaging (Pentacam HR, Oculus Optikger&auml;te GmbH, Wetzlar, Germany) using linear regression analysis to assess the associations of ACA in the different sectors with gestational age (GA), birth weight, birth weight percentile, retinopathy of prematurity (ROP), ROP treatment, placental insufficiency, preeclampsia, and breastfeeding. Results: In total, 516 eyes of 319 preterm and full-term individuals (aged 28.9 &plusmn; 8.8 years, 188 females) were examined. ROP treatment was associated with smaller ACA width in the nasal (B = &minus;9.6 [95%CI: &minus;14.7; &minus;4.5] degree; p &lt; 0.001) and temporal positions (B = &minus;11.5 [95%CI: &minus;17.7; &minus;5.3] degree; p = 0.001), whereas non-treated individuals with ROP had an unaltered ACA width, as did individuals with low gestational age without ROP. Conclusion: Advanced stages of ROP following treatment with laser- and cryocoagulation lead to a smaller ACA width until adulthood, and hence may increase the risk of angle closure in later life