Change in specific interactions between lactose repressor protein and DNA induced by ligand binding: molecular dynamics and molecular orbital calculations

<div><p>Lactose repressor protein (LacR) plays an essential role in controlling the transcription mechanism of genomic information from DNA to mRNA. It has been elucidated that a ligand binding to LacR regulates allosterically the specific interactions between LacR and operator DNA. However, the effect of the ligand binding on the specific interactions has not been clarified at an atomic level. In this study, we performed classical molecular dynamics (MD) and <i>ab initio</i> fragment molecular orbital simulations to elucidate the effect of ligand binding at atomic and electronic levels. The MD simulations for the solvated complexes with LacR-dimer, DNA and ligand demonstrate that the binding of an inducer IPTG to LacR-dimer significantly changes the structure of LacR-monomer to cause strong interactions between LacR-monomers, resulting in weakening the interactions between LacR-dimer and DNA. In contrast, the binding of an anti-inducer ONPF to LacR-dimer was found to enhance the interactions between LacR-dimer and DNA. These findings are consistent with the functions of IPTG and ONPF as an inducer and an anti-inducer, respectively. We therefore proposed a simplified model for the effect of the ligand binding on the specific interactions between LacR-dimer and DNA.</p></div

Blood Reference Intervals for Preterm Low-Birth-Weight Infants: A Multicenter Cohort Study in Japan

<div><p>Preterm low-birth-weight infants remain difficult to manage based on adequate laboratory tests. The aim of this study was to establish blood reference intervals (RIs) in those newborns who were admitted to and survived in the neonatal intensive care unit (NICU). A multicenter prospective study was conducted among all infants admitted to 11 affiliated NICUs from 2010 to 2013. The clinical information and laboratory data were registered in a network database designed for this study. The RIs for 26 items were derived using the parametric method after applying the latent abnormal values exclusion method. The influence of birth weight (BW) and gestational age (GA) on the test results was expressed in terms of the standard deviation ratio (SDR), as SDR_BW and SDR_GA, respectively. A total of 3189 infants were admitted during the study period; 246 were excluded due to a lack of blood sampling data, and 234 were excluded for chromosomal abnormalities (n = 108), congenital anomalies requiring treatment with surgical procedures (n = 76), and death or transfer to another hospital (n = 50). As a result, 2709 infants were enrolled in this study. Both the SDR_GA and SDR_BW were above 0.4 in the test results for total protein (TP), albumin (ALB), alanine aminotransferase (ALT), and red blood cells (RBC); their values increased in proportion to the BW and GA. We derived 26 blood RIs for infants who were admitted to NICUs. These RIs should help in the performance of proper clinical assessments and research in the field of perinatal-neonatal medicine.</p></div

GA-specific RIs of blood chemistry and hematology for preterm infants (International Unit).

<p>GA-specific RIs of blood chemistry and hematology for preterm infants (International Unit).</p

BW-specific RIs of blood chemistry and hematology for low-birth-weight infants (International Unit)

<p>BW-specific RIs of blood chemistry and hematology for low-birth-weight infants (International Unit)</p

Scatter plots of the items that were significant in both the SDR_GA and SDR_BW.

<p>The horizontal axis shows the birth weight (BW). The vertical axis shows the measured values of A. Total protein (g/dL), B. Albumin (g/dL), C. Alanine aminotransferace (ALT) (IU/L), and D. Red blood cells (10⁶/μl). The data were classified into three subgroups based on gestational age (GA): GA of 32–37 weeks, cross marks (×); 28–32 weeks, open circles (○); 22–28 weeks, filled circles (●).</p

Additional file 1: of Sustained endocrine profiles of a girl with WAGR syndrome

For cytogenetics, quantitative PCR for copy number and gene expression analyses, methylation analysis, and ethics statement. Figure S1. Neuro-endocrine profile of the present case. Table S1. Methylation profile of the present case. Additional file References 1–3. (PDF 652 kb