The secondary messenger ppGpp interferes with cAMP-CRP regulon by promoting CRP acetylation in Escherichia coli.

The cAMP-CRP regulon coordinates transcription regulation of several energy-related genes, the lac operon among them. Lactose, or IPTG, induces the lac operon expression by binding to the LacI repressor, and releasing it from the promoter sequence. At the same time, the expression of the lac operon requires the presence of the CRP-cAMP complex, which promotes the binding of the RNA polymerase to the promoter region.

Common infectious morbidity and white blood cell count in middle childhood predict behavior problems in adolescence.

We examined the associations of middle childhood infectious morbidity and inflammatory biomarkers with adolescent internalizing and externalizing behavior problems. We recruited 1018 Colombian schoolchildren aged 5-12 years into a cohort. We quantified white blood cell (WBC) counts and C-reactive protein at enrollment and prospectively recorded incidence of gastrointestinal, respiratory, and fever-associated morbidity during the first follow-up year.

Long-term stability of avalanche scaling and integrative network organization in prefrontal and premotor cortex.

Ongoing neuronal activity in the brain establishes functional networks that reflect normal and pathological brain function. Most estimates of these functional networks suffer from low spatiotemporal resolution and indirect measures of neuronal population activity, limiting the accuracy and reliability in their reconstruction over time. Here, we studied the stability of neuronal avalanche dynamics and corresponding reconstructed functional networks in the adult brain.

Burosumab treatment for fibrous dysplasia.

Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic disorder of Gα activation. Fibroblast Growth Factor 23 (FGF23)-mediated hypophosphatemia is a feature of FD/MAS that has been associated with poor skeletal outcomes. Standard therapy includes oral phosphorus and vitamin D analogs; however, treatment is limited by potential adverse renal and gastrointestinal effects.

Maternal exposure to a high-magnitude earthquake during pregnancy influences pre-reading skills in early childhood.

Exposure to an adverse prenatal environment can influence fetal development and result in long-lasting changes in the offspring. However, the association between maternal exposure to stressful events during pregnancy and the achievement of pre-reading skills in the offspring is unknown. Here we examined the association between prenatal exposure to the Chilean high-magnitude earthquake that occurred on February 27th, 2010 and the development of early reading precursors skills (listening comprehension, print knowledge, alphabet knowledge, vocabulary, and phonological awareness) in children at kindergarten age.

Leukocyte telomere length is inversely associated with a metabolic risk score in Mesoamerican children.

Objective: Leukocyte telomere length (LTL) may be involved in the etiology of the metabolic syndrome (MetS). We examined the associations of LTL with MetS and its components among Mesoamerican children and their adult parents, in a region where MetS prevalence is high.

Methods: We conducted a cross-sectional study of 151 children aged 7-12 years and 346 parents from the capitals of Belize, Honduras, Nicaragua, Costa Rica, Panama, and Chiapas State, Mexico.

Vitamin D status in infancy and cardiometabolic health in adolescence.

Background: Vitamin D deficiency is associated with obesity-related conditions, but the role of early life vitamin D status on the development of obesity is poorly understood.

Objectives: We assessed whether serum 25-hydroxyvitamin D [25(OH)D] at age 1 y was related to metabolic health through adolescence.

Methods: We quantified serum 25(OH)D in samples obtained at age 1 y from 306 participants in a cohort study in Santiago, Chile.

Design and Implementation of an Innovative Undergraduate Pediatric Clinical Experience With Teenagers of Mexican Heritage.

This article describes an innovative community-based pediatric clinical rotation for undergraduate nursing students. Students were charged with conducting interactive educational sessions on health-related topics of interest to participants in a six-week summer day camp for adolescents of Mexican heritage. At the completion of the experience, students identified social determinants of health that impacted the health of the community and the impact of the experience on their nursing practice.

Expansion of germline RPS20 mutation phenotype to include Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a ribosomopathy of variable expressivity and penetrance characterized by red cell aplasia, congenital anomalies, and predisposition to certain cancers, including early-onset colorectal cancer (CRC). DBA is primarily caused by a dominant mutation of a ribosomal protein (RP) gene, although approximately 20% of patients remain genetically uncharacterized despite exome sequencing and copy number analysis. Although somatic loss-of-function mutations in RP genes have been reported in sporadic cancers, with the exceptions of 5q-myelodysplastic syndrome (RPS14) and microsatellite unstable CRC (RPL22), these cancers are not enriched in DBA.

RNA abasic sites in yeast and human cells.

RNA abasic sites and the mechanisms involved in their regulation are mostly unknown; in contrast, DNA abasic sites are well-studied. We found surprisingly that, in yeast and human cells, RNA abasic sites are prevalent. When a base is lost from RNA, the remaining ribose is found as a closed-ring or an open-ring sugar with a reactive C1' aldehyde group.

Metformin improves blood glucose by increasing incretins independent of changes in gluconeogenesis in youth with type 2 diabetes.

Aims/hypothesis: Metformin is the only approved oral agent for youth with type 2 diabetes but its mechanism of action remains controversial. Recent data in adults suggest a primary role for the enteroinsular pathway, but there are no data in youth, in whom metformin efficacy is only ~50%. Our objectives were to compare incretin concentrations and rates of glucose production and gluconeogenesis in youth with type 2 diabetes before and after short-term metformin therapy compared with peers with normal glucose tolerance (NGT).

Fractures in children and adolescents living with perinatally acquired HIV.

Background: Across numerous settings, bone mineral density for age and sex is lower in children/adolescents living with perinatally-acquired HIV (PHIV) compared to uninfected peers. We assessed incidences of any fracture/any long bone fracture, and osteoporosis prevalence in PHIV and HIV-exposed uninfected (PHEU) participants in the Pediatric HIV/AIDS Cohort Study (PHACS).

Methodology: Lifetime history of fracture events from birth up to age 20 years was obtained by chart review and/or interview, including age at fracture, mechanism, and bone(s) fractured.

Safety and Efficacy of 48 and 96 Weeks of Alendronate in Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection and Low Bone Mineral Density for Age.

No safety concerns were identified in a randomized, crossover study of alendronate/placebo in youth with perinatal HIV infection and low bone mineral density (BMD). BMD improved with 48 weeks of alendronate and continued to improve with an additional 48 weeks of therapy. Gains were largely maintained 48 weeks after stopping alendronate.

Statins for Smith-Lemli-Opitz syndrome.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: 1. To evaluate the efficacy of statin therapy in reducing the frequency or severity of the neurobehavioral abnormalities seen in people with SLOS (e.

18F-FDOPA PET/CT accurately identifies MEN1-associated pheochromocytoma.

Summary: Pheochromocytoma (PHEO) in multiple endocrine neoplasia type 1 (MEN1) is extremely rare. The incidence is reported as less than 2%. We report a case of a 76-year-old male with familial MEN1 who was found to have unilateral PHEO.

Vitamin D and Reproductive Hormones Across the Menstrual Cycle.

Study Question: How do the calciotropic hormones (25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and intact parathyroid hormone (iPTH)) vary across the menstrual cycle and do cyclic patterns of reproductive hormones (estradiol, progesterone, LH, FSH) differ by vitamin D status?

Summary Answer: Calciotropic hormones vary minimally across the menstrual cycle; however, women with 25-hydroxyvitamin D below 30 ng/ml have lower mean estradiol across the menstrual cycle.

What Is Known Already: Prior human studies suggest that vitamin D status is associated with fecundability, but the mechanism is unknown. Exogenous estrogens and prolonged changes in endogenous estradiol (pregnancy or menopause) influence concentrations of 25-hydroxyvitamin D.

Quetiapine-Induced Central Hypothyroidism.

Hypothyroidism has been associated with quetiapine, but the underlying mechanism is not well understood and has been presumed to result from thyroid gland dysfunction (primary hypothyroidism). We present a case of symptomatic quetiapine-induced hypothyroidism due to hypothalamic/pituitary gland dysfunction (central [secondary] hypothyroidism).

A Combinatorial Strategy for Targeting -Mutant Cancers with BRAF Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib).

Purpose: Most aggressive thyroid cancers are commonly associated with a mutation. Preclinical and clinical data in cancers suggest that combined BRAF and MEK inhibitor treatment results in a response, but resistance is common. One mechanism of acquired resistance is through persistent activation of tyrosine kinase (TK) signaling by alternate pathways.

eIF1 discriminates against suboptimal initiation sites to prevent excessive uORF translation genome-wide.

The translation preinitiation complex (PIC) scans the mRNA for an AUG codon in a favorable context. Previous findings suggest that the factor eIF1 discriminates against non-AUG start codons by impeding full accommodation of Met-tRNA in the P site of the 40S ribosomal subunit, necessitating eIF1 dissociation for start codon selection. Consistent with this, yeast eIF1 substitutions that weaken its binding to the PIC increase initiation at UUG codons on a mutant mRNA and particular synthetic mRNA reporters; and also at the AUG start codon of the mRNA for eIF1 itself owing to its poor Kozak context.

Inflammasomes: Their Role in Normal and Complicated Pregnancies.

Inflammasomes are cytoplasmic multiprotein complexes that coordinate inflammatory responses, including those that take place during pregnancy. Inflammasomes and their downstream mediators caspase-1 and IL-1β are expressed by gestational tissues (e.g.

Triglyceride Paradox Is Related to Lipoprotein Size, Visceral Adiposity and Stearoyl-CoA Desaturase Activity in Black Versus White Women.

Rationale: In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index.

Objective: In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels.

Paternal bias expression of Igf2as is enhancer-dependent on the imprinting cluster of Igf2, H19 and Nctc1 in muscle cells.

Igf2, H19, and Nctc1 are linked co-regulated genes on distal mouse chromosome 7. This locus is an important model both for studying mechanisms of monoallelic expression and for elucidating the role of cis-regulatory elements - enhancers and insulators - in organizing chromatin and gene expression across a large domain. In this study we characterize regulated expression of the Igf2 antisense transcript (Igf2as) in primary muscle cells.

Long-Term Neuropsychological Outcomes from an Open-Label Phase I/IIa Trial of 2-Hydroxypropyl-β-Cyclodextrins (VTS-270) in Niemann-Pick Disease, Type C1.

Background: Niemann-Pick disease, type C1 (NPC1) is a neurodegenerative condition that arises from mutations of NPC1 and is often diagnosed in children. Recently, several drug trials have been implemented to minimize neurodegeneration, including a trial of 2-hydroxypropyl-β-cyclodextrins (VTS-270).

Objectives: The current study extends findings from a previous report of 18 months of disease severity data by describing neuropsychological outcomes over the course of 36 months post-baseline.