Supplementary Material for: The Neonatal Microbiome and Its Partial Role in Mediating the Association between Birth by Cesarean Section and Adverse Pediatric Outcomes

<b><i>Background:</i></b> Cesarean sections (CS) are among the most commonly performed surgical procedures in the world. Epidemiologic data has associated delivery by CS with an increased risk of certain adverse health outcomes in children, such as asthma and obesity. <b><i>Objective:</i></b> To explore what is known about the effect of mode of delivery on the development of the infant microbiome and discuss the potentially mediating role of CS-related microbial dysbiosis in the development of adverse pediatric health outcomes. Recommendations for future inquiry are also provided. <b><i>Methods:</i></b> This study provides a narrative overview of the literature synthesizing the findings of literature retrieved from searches of PubMed and other computerized databases and authoritative texts. <b><i>Results:</i></b> Emerging evidence suggests that mode of delivery is involved in the development of the neonatal microbiome and may partially explain pediatric health outcomes associated with birth by CS. Specifically, the gut microbiome of vaginally delivered infants more closely resembles their mothers’ vaginal microbiome and thus more commonly consists of potentially beneficial microbiota such as <i>Lactobacillus</i>,<i> Bifidobacterium</i>, and <i>Bacteroides</i>. Conversely, the microbiome of infants born via CS shows an increased prevalence of either skin flora or potentially pathogenic microbial communities such as <i>Klebsiella</i>, <i>Enterococcus</i>, and <i>Clostridium</i>. <b><i>Conclusions:</i></b> Mode of delivery plays an important role in the development of the postnatal microbiome but likely tells only part of the story. More comprehensive investigations into all the pre- and perinatal factors that have the potential to contribute to the neonatal microbiome are warranted

Clonal immunoglobulin DNA in the plasma of patients with AIDS lymphoma

Immunoglobulin (Ig) gene rearrangements are used to define clonality of suspected B-lineage malignancy in tissue samples. To determine whether such rearrangements could be identified in plasma, we screened plasma from 14 consecutive patients with AIDS-related lymphoma with multiplex Ig primers. Clonally rearranged Ig DNA was detected in plasma from 7 of 14 patients. Patients in whom clonal Ig DNA remained detectable after combination chemotherapy died with lymphoma. Tumor was available from 1 patient, and the IgH amplification products from plasma and tumor were sequenced and confirmed to be identical. Ig DNA rearrangements in plasma may be useful as a lymphoma-specific tumor marker, and failure to clear clonal Ig DNA may identify patients at high risk for failure of standard therapy

Mutation of a conserved proline residue in the beta-subunit ectodomain prevents Na(+)-K(+)-ATPase oligomerization

A highly conserved sequence motif (4 tyrosines and 1 proline: YYPYY) of the Na(+)-K(+)-adenosinetriphosphatase (ATPase) beta 1-subunit ectodomain has been mutagenized to study its possible role in alpha/beta-assembly and sodium pump function. Single as well as double tyrosine mutants (tyrosine to phenylalanine: Y to F) of Xenopus laevis beta 1-subunits are able to associate with alpha 1-subunits and form functional Na-K pumps at the plasma membrane that are indistinguishable from wild-type alpha 1, beta 1-Na-K pumps (as assessed by measurements of ouabain binding, 86Rb flux, Na-K pump current, and activation by external potassium). In contrast, a single proline mutation (proline to glycine: P244G) reduced by &gt; 90% the proper assembly and function of Na(+)-K(+)-ATPase, despite a normal rate of synthesis and core glycosylation. Our data indicate that proline-244 plays a critical role in the proper folding of the beta-subunit and its ability to associate efficiently with the alpha 1-subunit in the endoplasmic reticulum