Association between short sleep duration and the risk of sensitization to food and aero allergens in rural Chinese adolescents.

Background: Both long and short sleep duration have been associated with obesity, cardiovascular disease, and diabetes. However, there have been no previous studies investigating the potential relationship between altered sleep duration and allergen sensitization.

Objective: To explore the association between sleep duration and sensitization to food and aeroallergens.

Mouse survival motor neuron alleles that mimic SMN2 splicing and are inducible rescue embryonic lethality early in development but not late.

Spinal muscular atrophy (SMA) is caused by low survival motor neuron (SMN) levels and patients represent a clinical spectrum due primarily to varying copies of the survival motor neuron-2 (SMN2) gene. Patient and animals studies show that disease severity is abrogated as SMN levels increase. Since therapies currently being pursued target the induction of SMN, it will be important to understand the dosage, timing and cellular requirements of SMN for disease etiology and potential therapeutic intervention.

BTECH: a platform to integrate genomic, transcriptomic and epigenomic alterations in brain tumors.

The identification of molecular signatures predictive of clinical behavior and outcome in brain tumors has been the focus of many studies in the recent years. Despite the wealth of data that are available in the public domain on alterations in the genome, epigenome and transcriptome of brain tumors, the underlying molecular mechanisms leading to tumor initiation and progression remain largely unknown. Unfortunately, most of these data are scattered in multiple databases and supplementary materials of publications, thus making their retrieval, evaluation, comparison and visualization a rather arduous task.

DataGenno: building a new tool to bridge molecular and clinical genetics.

Clinical genetics is one of the most challenging fields in medicine, with thousands of children born every year with congenital defects that have no satisfactory diagnosis. There are more than 6,000 known single-gene disorders that can cause birth defects or diseases in approximately 1 in every 200 births. Clinical and molecular information on genetic diseases and syndromes are widespread in the literature, and there are few databases combining this information.

Epigenomics in cancer management.

The identification of all epigenetic modifications implicated in gene expression is the next step for a better understanding of human biology in both normal and pathological states. This field is referred to as epigenomics, and it is defined as epigenetic changes (ie, DNA methylation, histone modifications and regulation by noncoding RNAs such as microRNAs) on a genomic scale rather than a single gene. Epigenetics modulate the structure of the chromatin, thereby affecting the transcription of genes in the genome.

Non-coding RNAs: could they be the answer?

Despite a considerable amount of effort by different groups to evaluate the genetic traits associated with complex diseases by genome-wide association studies (GWAS), just a few regions, mainly linked to protein-coding genes, were identified. Recently, studies from different groups have implicated new classes of long non-coding RNAs (ncRNAs) to important molecular mechanisms. Additionally, high-throughput transcriptome analyses of different cell types have shown that an unexpected amount of genomic DNA is transcribed.

Regulation of the embryonic morphogen Nodal by Notch4 facilitates manifestation of the aggressive melanoma phenotype.

Metastatic melanoma is an aggressive skin cancer associated with poor prognosis. The reactivation of the embryonic morphogen Nodal in metastatic melanoma has previously been shown to regulate the aggressive behavior of these tumor cells. During the establishment of left-right asymmetry in early vertebrate development, Nodal expression is specifically regulated by a Notch signaling pathway.

Balanced Shh signaling is required for proper formation and maintenance of dorsal telencephalic midline structures.

Background: The rostral telencephalic dorsal midline is an organizing center critical for the formation of the future cortex and hippocampus. While the intersection of WNTs, BMPs, and FGFs establishes boundaries within this critical center, a direct role of Shh signaling in this region remains controversial. In this paper we show that both increased and decreased Shh signaling directly affects boundary formation within the telencephalic dorsal midline.

Does genetic regulation of IgE begin in utero? Evidence from T(H)1/T(H)2 gene polymorphisms and cord blood total IgE.

Background: Elucidation of early life factors is critical to understand the development of allergic diseases, especially those manifesting in early life such as food allergies and atopic dermatitis. Cord blood IgE (CBIgE) is a recognized risk factor for the subsequent development of allergic diseases. In contrast with numerous genetic studies of total serum IgE in children and adults, limited genetic studies on CBIgE have been conducted.

Pdlim7 is required for maintenance of the mesenchymal/epidermal Fgf signaling feedback loop during zebrafish pectoral fin development.

Background: Vertebrate limb development involves a reciprocal feedback loop between limb mesenchyme and the overlying apical ectodermal ridge (AER). Several gene pathways participate in this feedback loop, including Fgf signaling. In the forelimb lateral plate mesenchyme, Tbx5 activates Fgf10 expression, which in turn initiates and maintains the mesenchyme/AER Fgf signaling loop.

RNA editing is absent in a single mitochondrial gene of Didymium iridis.

An open reading frame (ORF) was found in the mitochondrial genome of the Pan2-16 strain of Didymium iridis that showed high similarity to the NADH dehydrogenase subunit 3 (nad3) gene in other organisms. So far all other typical mitochondrial genes identified in this organism require RNA editing to generate ORFs capable of directing protein synthesis. The D.

Integrins modulate cellular fibrogenesis at multiple levels; Regulation of TGF-β signaling.

Fibrosis could occur in virtually any organ or tissue. The fibrotic lesion indolently disrupts the structure of the healthy organ, thereby hampering its proper function, consequence of which is devastating. Among the myriad factors that modulate fibrogenesis, transforming growth factor β (TGF-β) is one of the most studied and its central role for fibrotic disorders has been strongly suggested.

Folic acid remodels chromatin on Hes1 and Neurog2 promoters during caudal neural tube development.

The mechanism(s) behind folate rescue of neural tube closure are not well understood. In this study we show that maternal intake of folate prior to conception reverses the proliferation potential of neural crest stem cells in homozygous Splotch embryos (Sp(-/-)) via epigenetic mechanisms. It is also shown that the pattern of differentiation seen in these cells is similar to wild-type (WT).

The roles of chondroitin-4-sulfotransferase-1 in development and disease.

The glycosaminoglycan chondroitin sulfate (CS) consists of long linear chains of repeating disaccharide units, which are covalently attached to core proteins to form CS-proteoglycans. These molecules have been shown to fulfill important biological functions in development, disease, and signaling. Biosynthesis of CS takes place in the Golgi apparatus.

Development of electrocardiogram intervals during growth of FVB/N neonate mice.

Background: Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates.

Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice.

Proximal spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Traditionally, SMA has been described as a motor neuron disease; however, there is a growing body of evidence that arrhythmia and/or cardiomyopathy may present in SMA patients at an increased frequency. Here, we ask whether SMA model mice possess such phenotypes.

Genetic and environmental influences on serum lipid tracking: a population-based, longitudinal Chinese twin study.

We conducted cross-sectional and longitudinal twin analysis to explore genetic and environmental contribution to serum lipid tracking during childhood and adolescence. The study sample was part of a population-based twin cohort that was recruited in the rural areas of the Anhui Province of China. The baseline recruitment of twins was carried out from 1998 through 2000 and the follow-up from 2005 through 2007.

New insights into cathepsin D in mammary tissue development and remodeling.

Cathepsin D (CatD) is a lysosomal aspartyl endopeptidase originally considered a "house keeping enzyme" involved in the clearance of unwanted proteins. However, recent studies have revealed CatD's involvement in apoptosis and autophagy, thus signifying an important function in the proper development and maintenance of multi-cellular organs. In the mammary gland, matrix degradation and the remodeling process are orchestrated by proteolytic enzymes, but the role of CatD at distinct developmental stages has remained mostly unexplored.

Cancer hallmarks in induced pluripotent cells: new insights.

Studies are beginning to emerge that demonstrate intriguing differences between human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). Here, we investigated the expression of key members of the Nodal embryonic signaling pathway, critical to the maintenance of pluripotency in hESCs. Western blot and real-time RT-PCR analyses reveal slightly lower levels of Nodal (a TGF-beta family member) and Cripto-1 (Nodal's co-receptor) and a dramatic decrease in Lefty (Nodal's inhibitor and TGF-beta family member) in hiPSCs compared with hESCs.

Glial cell line-derived neurotrophic factor-secreting genetically modified human bone marrow-derived mesenchymal stem cells promote recovery in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of nigrostriatal dopaminergic (DA) neurons. The therapeutic potential of glial cell line-derived neurotrophic factor (GDNF), the most potent neurotrophic factor for DA neurons, has been demonstrated in many experimental models of PD. However, chronic delivery of GDNF to DA neurons in the brain remains an unmet challenge.

Non-coding RNAs: Meet thy masters.

New DNA sequencing technologies have provided novel insights into eukaryotic genomes, epigenomes, and the transcriptome, including the identification of new non-coding RNA (ncRNA) classes such as promoter-associated RNAs and long RNAs. Moreover, it is now clear that up to 90% of eukaryotic genomes are transcribed, generating an extraordinary range of RNAs with no coding capacity. Taken together, these new discoveries are modifying the status quo in genomic science by demonstrating that the eukaryotic gene pool is divided into two distinct categories of transcripts: protein-coding and non-coding.

Novel mechanism of fetal hepatocyte injury in congenital alloimmune hepatitis involves the terminal complement cascade.

Unlabelled: Evidence suggests that most neonatal hemochromatosis (NH) is the phenotypic expression of gestational alloimmune fetal liver injury. Gestational alloimmune diseases are induced by the placental passage of specific reactive immunoglobulin G and often involve the activation of fetal complement by the classical pathway leading to the formation of membrane attack complex (MAC) as the effector of cell injury. We examined liver specimens from cases of NH, from cases of non-NH liver disease, and from infants without liver disease to determine if they would provide evidence that MAC is involved in hepatocyte injury.

Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells.

Objective: To investigate the distribution of mast cells and dendritic cell (DC) subsets in paired muscle and skin (lesional/nonlesional) from untreated children with juvenile dermatomyositis (DM).

Methods: Muscle and skin biopsy samples (4 skin biopsy samples with active rash) from 7 patients with probable/definite juvenile DM were compared with muscle and skin samples from 10 healthy pediatric controls. Mast cell distribution and number were assessed by toluidine blue staining and analyzed by Student's t-test.