Mean outcome distribution according to genotype and phenotype.

*<p>Surgery for necrotizing enterocolitis.</p

Hypertrophy and hypotrophy and clinical data in German vlbw infant population.

<p>Hypertrophy and hypotrophy and clinical data in German vlbw infant population.</p

Table 1. Genotypic and phenotypic characterisation of investigated individuals.

<p>Table 1. Genotypic and phenotypic characterisation of investigated individuals.</p

Mitochondrial function.

<p>(A) Basal ATP synthesis rates. The assay demonstrated a significant reduction in ATP production in the <i>Parkin</i>-mutant patients (median [IQR]: 39% [23%, 55%]) compared to controls (set to 100%). (B) Basal ATP levels. Quantifying the overall cellular ATP concentration showed significantly lower levels in the mutants (median [IQR]: 69% [58%, 75%]) than in controls (set to 100%). (C) Mitochondrial membrane potential under basal and oxidative stress conditions. Control (median [IQR]: 100% [94%, 115%]) and patient fibroblasts (median [IQR]: 113% [93%, 128%]) with <i>Parkin</i> mutations show similar membrane potential under basal conditions. When the cells were treated with paraquat (shaded boxes), no relevant changes were detected in the controls (median [IQR]: 102% [100%, 118%]). In the <i>Parkin</i> mutants, a significant drop of the membrane potential was observed (median [IQR]: 84% [81%, 103%]). The median, the interquartile range (IQR), the minimum and the maximum value of 6 (A) or 4 (B) independent experimental runs are plotted. In each experimental run the average ATP level in the controls was set to 100%.</p

Protein oxidation under basal and stress conditions.

<p>Oxidation of proteins in <i>Parkin</i>-mutant fibroblasts and controls was determined by means of an OxyBlot. (A) When quantifying the protein oxidation in each individual using an antibody against DNP, the <i>Parkin</i> mutants (median [IQR]: 123% [113%, 136%]) showed significantly higher levels of oxidation than the controls (median [IQR]: 100% [97%, 105%]). After treatment of the cells with paraquat (shaded boxes), the difference in oxidation between mutants (median [IQR]: 131% [96%, 172%]) and controls (median [IQR]: 100% [90%, 102%]) increased, but was no longer significant. Equal protein loading was verified with an antibody against β-actin. Expression ratios of oxidized proteins vs. β-actin were calculated. The median, the interquartile range (IQR), the minimum and the maximum value of the investigated groups of individuals are given. (B) OxyBlot of pooled protein samples before and after paraquat treatment showing a similar trend as identified by individual measurements.</p

Morphology of the mitochondrial network.

<p>(A) Images of the mitochondrial network in control and patient fibroblasts demonstrating similar degrees of branching under basal culturing conditions. (B) After treatment with paraquat, the network was less branched in patients and controls. (C) The degree of mitochondrial branching (form factor) was comparable in patients (median [IQR]: 78% [66%, 90%]) and controls (median [IQR]: 100% [73%, 105%]) under standard cell culturing conditions. When treated with paraquat (shaded boxes), the form factor decreased significantly in the mutant samples (median [IQR]: 46% [43%, 54%]). By contrast, a drop seen in controls (median [IQR]: 70% [32%, 84%]) was not significant. (D) Citrate synthase activity in cell lysates. <i>Parkin</i> mutants (median [IQR]: 183% [125%, 232%]) showed significantly higher citrate synthase activities than controls (median [IQR]: 100% [43%, 101%]), indicative of increased mitochondrial mass per cell in the former. Citrate synthase activity in cell lysates was normalized for protein concentration. The median, the interquartile range (IQR), the minimum and the maximum value of the investigated groups of individuals are shown.</p

Outcome of patients in microclusters of blood-culture proven sepsis.

<p><b>Legend:</b> IVH intraventricular haemorrhage; Surgery for PDA Patent Ductus arteriosus, NEC necrotizing enterocolitis, FIP focal intestinal perforation, ROP retinopathy of prematurity (kryo- or laser therapy); BPD bronchopulmonary dysplasia; severe complication: IVH grade IV, posthaemorrhagic hydrocephalus with need for VP shunt, periventricular leukomalacia, surgery for NEC/FIP or ROP and BPD;</p><p>p-values were derived from chi-square test if not otherwise indicated (* Mann-Whitney-U test comparing linked cases vs. first patient in cluster.</p

Pathogenic spectrum of blood-culture proven sepsis episodes.

*<p>Estimate: estimated risk for specific pathogen/100 cases of blood-culture proven sepsis.</p

Clinical characteristics of the VLBW cohort stratified to occurrence of late-onset sepsis (LOS).

<p><b>Legend:</b> PPROM Preterm premature rupture of membranes, C/section Caesarean section, SGA small-for-gestational-age (<10th Voigt percentile).</p><p># p-values were derived from chi-square test if not otherwise indicated (* Mann-Whitney-U test).</p