Causal mediation analysis with a latent mediator.

Health researchers are often interested in assessing the direct effect of a treatment or exposure on an outcome variable, as well as its indirect (or mediation) effect through an intermediate variable (or mediator). For an outcome following a nonlinear model, the mediation formula may be used to estimate causally interpretable mediation effects. This method, like others, assumes that the mediator is observed.

Clinical Effectiveness of Modified Laparoscopic Fimbrioplasty for the Treatment of Minimal Endometriosis and Unexplained Infertility.

Objective. To study the reproductive outcomes of modified laparoscopic fimbrioplasty (MLF), a surgical technique designed to increase the working surface area of the fimbriated end of the fallopian tube. We postulated that an improvement in fimbrial function through MLF will improve reproductive outcomes.

Calcium-mediated histone modifications regulate alternative splicing in cardiomyocytes.

In cardiomyocytes, calcium is known to control gene expression at the level of transcription, whereas its role in regulating alternative splicing has not been explored. Here we report that, in mouse primary or embryonic stem cell-derived cardiomyocytes, increased calcium levels induce robust and reversible skipping of several alternative exons from endogenously expressed genes. Interestingly, we demonstrate a calcium-mediated splicing regulatory mechanism that depends on changes of histone modifications.

Increased number of teeth predict acquisition of mutans streptococci in infants.

This longitudinal study of 194 very-low birthweight (VLBW) and 184 normal birthweight (NBW) infants hypothesized that the causal pathway between birth group (VLBW or NBW) and mutans streptococci (MS) acquisition (presence) at 18-20 months is mediated by biological, behavioral, and caregiver MS levels. Biological (number of teeth at 8 and 18-20 months and enamel hypoplasia) and behavioral (brushing/cleaning, sweet snacks, breastfeeding, and dental access) factors were assessed using dental examinations and caregiver questionnaire responses at 8 and 18-20 months. Infant MS acquisition and caregiver MS levels were assessed from saliva and plaque samples collected at 8 and 18-20 months.

The p97-UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated HuR from mRNP.

The assembly and disassembly of ribonucleoproteins (RNPs) are dynamic processes that control every step of RNA metabolism, including mRNA stability. However, our knowledge of how RNP remodeling is achieved is largely limited to RNA helicase functions. Here, we report a previously unknown mechanism that implicates the ATPase p97, a protein-remodeling machine, in the dynamic regulation of mRNP disassembly.

Alternative splicing of the neurofibromatosis type 1 pre-mRNA is regulated by the muscleblind-like proteins and the CUG-BP and ELAV-like factors.

Background: Alternative splicing is often subjected to complex regulatory control that involves many protein factors and cis-acting RNA sequence elements. One major challenge is to identify all of the protein players and define how they control alternative expression of a particular exon in a combinatorial manner. The Muscleblind-like (MBNL) and CUG-BP and ELAV-Like family (CELF) proteins are splicing regulatory proteins, which function as antagonists in the regulation of several alternative exons.

Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA-dependent manner.

Recent studies have provided strong evidence for a regulatory link among chromatin structure, histone modification, and splicing regulation. However, it is largely unknown how local histone modification patterns surrounding alternative exons are connected to differential alternative splicing outcomes. Here we show that splicing regulator Hu proteins can induce local histone hyperacetylation by association with their target sequences on the pre-mRNA surrounding alternative exons of two different genes.