Rapamycin increases oxidative stress response gene expression in adult stem cells.

Balancing quiescence with proliferation is of paramount importance for adult stem cells in order to avoid hyperproliferation and cell depletion. In some models, stem cell exhaustion may be reversed with the drug rapamycin, which was shown can suppress cellular senescencein vitro and extend lifespan in animals. We hypothesized that rapamycin increases the expression of oxidative stress response genes in adult stem cells, and that these gene activities diminish with age.

Nodal expression and detection in cancer: experience and challenges.

Nodal is a TGF-β-related embryonic morphogen that is expressed in multiple human cancers. Detection of Nodal expression in these tissues can be challenging if issues related to Nodal transcription and protein processing are not considered. Here, we discuss certain characteristics related to Nodal expression and function and how these can facilitate acquisition and interpretation of expression data, contributing to our understanding of the potential role of Nodal in human cancer.

Molecular pathways: vasculogenic mimicry in tumor cells: diagnostic and therapeutic implications.

Tumor cell vasculogenic mimicry (VM) describes the functional plasticity of aggressive cancer cells forming de novo vascular networks, thereby providing a perfusion pathway for rapidly growing tumors, transporting fluid from leaky vessels, and/or connecting with endothelial-lined vasculature. The underlying induction of VM seems to be related to hypoxia, which may also promote the plastic, transendothelial phenotype of tumor cells capable of VM. Since its introduction in 1999 as a novel paradigm for melanoma tumor perfusion, many studies have contributed new insights into the underlying molecular pathways supporting VM in a variety of tumors, including melanoma, glioblastoma, carcinomas, and sarcomas.

Assessing teratogenic changes in a zebrafish model of fetal alcohol exposure.

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, including mental retardation due to disordered and damaged brain development. Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of birth defects that occur due to maternal alcohol consumption, and occurs in approximately 4% of children born in the United States.

Putative multifunctional signature of lung metastases in dedifferentiated chondrosarcoma.

Chondrosarcomas are among the most malignant skeletal tumors. Dedifferentiated chondrosarcoma is a highly aggressive subtype of chondrosarcoma, with lung metastases developing within a few months of diagnosis in 90% of patients. In this paper we performed comparative analyses of the transcriptomes of five individual metastatic lung lesions that were surgically resected from a patient with dedifferentiated chondrosarcoma.

Mapping mouse hemangioblast maturation from headfold stages.

The mouse posterior primitive streak at neural plate/headfold stages (NP/HF, ~7.5 dpc-8 dpc) represents an optimal window from which hemangioblasts can be isolated. We performed immunohistochemistry on this domain using established monoclonal antibodies for proteins that affect blood and endothelial fates.

Motor neuron rescue in spinal muscular atrophy mice demonstrates that sensory-motor defects are a consequence, not a cause, of motor neuron dysfunction.

The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has perinatal lethality, decreased motor function, motor unit pathology, and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves all phenotypes and pathologies commonly described in SMA mice.

Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration.

During forelimb regeneration in the newt Notophthalmus viridescens, the dynamic expression of a transitional matrix rich in hyaluronic acid, tenascin-C, and fibronectin controls muscle cell behavior in vivo and in vitro. However, the influence of extracellular matrix (ECM) remodeling on tissue stiffness and the cellular response to mechanical variations during regeneration was unknown. By measuring the transverse stiffness of tissues in situ, we found undifferentiated regenerative blastemas were less stiff than differentiated stump muscle (13.

Salamanders and fish can regenerate lost structures--why can't we?

The recent introduction of in vivo lineage-tracing techniques using fluorescently labeled cells challenged the long-standing view that complete dedifferentiation is a major force driving vertebrate tissue regeneration. The report in BMC Developmental Biology by Juan Carlos Izpisúa Belmonte and colleagues adds a new twist to a rapidly evolving view of the origin of blastemal cells. As classic and recent experimental findings are considered together, a new perspective on vertebrate muscle regeneration is emerging.

Minocycline attenuates microglia activation and blocks the long-term epileptogenic effects of early-life seizures.

Innate immunity mediated by microglia appears to play a crucial role in initiating and propagating seizure-induced inflammatory responses. To address the role of activated microglia in the pathogenesis of childhood epilepsy, we first examined the time course of microglia activation following kainic acid-induced status epilepticus (KA-SE) in Cx3cr1(GFP/+) transgenic mice whose microglia are fluorescently labeled. We then determined whether this seizure-induced microglia activation primes the central immune response to overreact and to increase the susceptibility to a second seizure later in life.

Three dimensional visualization and fractal analysis of mosaic patches in rat chimeras: cell assortment in liver, adrenal cortex and cornea.

The production of organ parenchyma in a rapid and reproducible manner is critical to normal development. In chimeras produced by the combination of genetically distinguishable tissues, mosaic patterns of cells derived from the combined genotypes can be visualized. These patterns comprise patches of contiguously similar genotypes and are different in different organs but similar in a given organ from individual to individual.

Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease.

Background & Aims: Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux.

A Parallel Study of mRNA and microRNA Profiling of Peripheral Blood in Young Adult Women.

Background: Aging is a complex process that involves the interplay of genetic, epigenetic, and environmental factors. Identifying aging-related biomarkers holds great potential for improving our understanding of complex physiological changes, thereby providing a means to investigate the mechanism by which aging influences various diseases.

Method And Results: We performed a parallel study of microRNA and gene expression profiling of peripheral blood in a group of healthy young adult women, among which 13 were aged 22-25 and 9 were aged 36-39 years old.

Transcriptional regulation of CFTR gene expression.

Cystic Fibrosis results from mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene was identified in 1989, but more than 20 years later, the regulatory mechanisms controlling its complex expression are still not fully understood. Though the promoter binds transcription factors and drives some aspects of CFTR gene expression, it cannot alone account for tissue specific control.

Genetic and epigenetic variations contributed by Alu retrotransposition.

Background: De novo retrotransposition of Alu elements has been recognized as a major driver for insertion polymorphisms in human populations. In this study, we exploited Alu-anchored bisulfite PCR libraries to identify evolutionarily recent Alu element insertions, and to investigate their genetic and epigenetic variation.

Results: A total of 327 putatively recent Alu insertions were identified, altogether represented by 1,762 sequence reads.

A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function.

Background: Distal cell-type-specific regulatory elements may be located at very large distances from the genes that they control and are often hidden within intergenic regions or in introns of other genes. The development of methods that enable mapping of regions of open chromatin genome wide has greatly advanced the identification and characterisation of these elements.

Methods: Here we use DNase I hypersensitivity mapping followed by deep sequencing (DNase-seq) to generate a map of open chromatin in primary human tracheal epithelial (HTE) cells and use bioinformatic approaches to characterise the distribution of these sites within the genome and with respect to gene promoters, intronic and intergenic regions.

Tracking blood glucose and predicting prediabetes in Chinese children and adolescents: a prospective twin study.

We examined the tracking of blood glucose, the development of prediabetes, and estimated their genetic contributions in a prospective, healthy, rural Chinese twin cohort. This report includes 1,766 subjects (998 males, 768 females) aged 6-21 years at baseline who completed a 6-year follow-up study. Oral glucose tolerance test was performed for all subjects at both baseline and follow-up.

Planar cell polarity signaling in craniofacial development.

Out of the several signaling pathways controlling craniofacial development, the role of planar cell polarity (PCP) signaling is relatively poorly understood. This pathway, originally identified as a mechanism to maintain cell polarity within the epithelial cells of the Drosophila wing, has been linked to the proper development of a wide variety of tissues in vertebrates and invertebrates. While many of the pathway members are conserved, it appears that some of the members of the pathway act in a tissue-specific manner.

Maternal intake of folic acid and neural crest stem cells.

Maternal folic acid (FA) intake has beneficial effects in preventing neural tube defects and may also play a role in the prevention of adult onset diseases such as Alzheimer's disease, dementia, neuropsychiatric disorders, cardiovascular diseases, and cerebral ischemia. This review will focus on the effects of maternal FA intake on neural crest stem cell proliferation and differentiation. Although FA is generally considered beneficial, it has the potential of promoting cell proliferation at the expense of differentiation.

Identification of microRNAs as potential prognostic markers in ependymoma.

Introduction: We have examined expression of microRNAs (miRNAs) in ependymomas to identify molecular markers of value for clinical management. miRNAs are non-coding RNAs that can block mRNA translation and affect mRNA stability. Changes in the expression of miRNAs have been correlated with many human cancers.

Inclusion of a portion of the native SNCA 3'UTR reduces toxicity of human S129A SNCA on striatal-projecting dopamine neurons in rat substantia nigra.

Experimental models of Parkinson's disease (PD) created by aberrant expression of the alpha-synuclein (SNCA) coding region have been reported. However, noncoding regions function in normal physiology and recent in vitro studies have shown that microRNAs-7 and -153 regulate SNCA expression by binding the 3'UTR. Here, effects of different hSNCA forms were examined in vivo.

Role of African ancestry and gene-environment interactions in predicting preterm birth.

Objective: To estimate whether African ancestry, specific gene polymorphisms, and gene-environment interactions could account for some of the unexplained preterm birth variance within African American women.

Methods: We genotyped 1,509 African ancestry-informative markers, cytochrome P450 1A1 (CYP1A1), and glutathione S-transferases Theta 1 (GSTT1) variants in 1,030 self-reported African American mothers. We estimated the African ancestral proportion using the ancestry-informative markers for all 1,030 self-reported African American mothers.

Nucleosome occupancy reveals regulatory elements of the CFTR promoter.

Access to regulatory elements of the genome can be inhibited by nucleosome core particles arranged along the DNA strand. Hence, sites that are accessible by transcription factors may be located by using nuclease digestion to identify the relative nucleosome occupancy of a genomic region. In order to define novel cis regulatory elements in the ∼2.

Short sleep duration is associated with insulin resistance independent of adiposity in Chinese adult twins.

Objective: To investigate the association between sleep duration and insulin resistance in rural Chinese adults and examine whether any such associations are independent of adiposity.

Methods: This is a cross-sectional analysis of 854 men and 640 women aged 20 to 70 years from the Anqing Twin Cohort. The following measures were obtained for each subject: Body mass index (BMI) and percentage of trunk fat (%TF), fasting plasma glucose, homeostatic model assessment of insulin resistance index (HOMA-IR), self-reported sleep duration and measures of snoring and sleep disturbance from the Pittsburgh Sleep Quality Indices (PSQI) questionnaire were modified for a Chinese population.

Epigenetic regulation of sensory neurogenesis in the dorsal root ganglion cell line ND7 by folic acid.

The epigenetic mechanism of folic acid (FA) action on dorsal root ganglion (DRG) cell proliferation and sensory neuron differentiation is not well understood. In this study, the ND7 cell line, derived from DRG cells, was used to elucidate this mechanism. In ND7 cells differentiated with dbcAMP and NGF, Hes1 and Pax3 levels decreased, whereas Neurog2 levels showed a modest increase.