DMLS: an automated pipeline to extract the Drosophila modular transcription regulators and targets from massive literature articles.

Transcription regulation in multicellular species is mediated by modular transcription factor (TF) binding site combinations termed cis-regulatory modules (CRMs). Such CRM-mediated transcription regulation determines the gene expression patterns during development. Biologists frequently investigate CRM transcription regulation on gene expressions.

Identifying Human miRNA Target Sites via Learning the Interaction Patterns between miRNA and mRNA Segments.

miRNAs (microRNAs) target specific mRNA (messenger RNA) sites to regulate their translation expression. Although miRNA targeting can rely on seed region base pairing, animal miRNAs, including human miRNAs, typically cooperate with several cofactors, leading to various noncanonical pairing rules. Therefore, identifying the binding sites of animal miRNAs remains challenging.

Gut-inhabiting Clostridia build human GPCR ligands by conjugating neurotransmitters with diet- and human-derived fatty acids.

Human physiology is regulated by endogenous signalling compounds, including fatty acid amides (FAAs), chemical mimics of which are made by bacteria. The molecules produced by human-associated microbes are difficult to identify because they may only be made in a local niche or they require a substrate sourced from the host, diet or other microbes. We identified a set of uncharacterized gene clusters in metagenomics data from the human gut microbiome.

The Effect of Processing Donor Milk on Its Nutrient and Energy Content.

The pasteurization is a mandatory step to inactivate pathogenic microorganisms of bank milk. For storage, freezing and thawing are necessary. The concentration of macronutrients and energy of bank milk could be influenced by these procedures which are routinely used in human milk bank.

A Pressure Test to Make 10 Molecules in 90 Days: External Evaluation of Methods to Engineer Biology.

Centralized facilities for genetic engineering, or "biofoundries", offer the potential to design organisms to address emerging needs in medicine, agriculture, industry, and defense. The field has seen rapid advances in technology, but it is difficult to gauge current capabilities or identify gaps across projects. To this end, our foundry was assessed via a timed "pressure test", in which 3 months were given to build organisms to produce 10 molecules unknown to us in advance.

The prognostic value of C-X-C motif chemokine receptor 4 in patients with sporadic malignant peripheral nerve sheath tumors.

Background: Recent studies indicate that C-X-C motif chemokine receptor 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibromatosis 1-associated malignant peripheral nerve sheath tumor (MPNST) cells and promote their proliferation. In this study, we measured the expression of CXCR4, CXCL12, and Cyclin D1 proteins in sporadic MPNST tissues from Chinese patients and investigated their prognostic values.

Methods: CXCR4, CXCL12, and Cyclin D1 protein expression in samples from 58 Chinese patients with sporadic MPNST was assessed with immunohistochemical staining.

Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases.

The gut microbiota modulate host biology in numerous ways, but little is known about the molecular mediators of these interactions. Previously, we found a widely distributed family of nonribosomal peptide synthetase gene clusters in gut bacteria. Here, by expressing a subset of these clusters in Escherichia coli or Bacillus subtilis, we show that they encode pyrazinones and dihydropyrazinones.

Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters.

Large-scale sequencing of prokaryotic (meta)genomic DNA suggests that most bacterial natural product gene clusters are not expressed under common laboratory culture conditions. Silent gene clusters represent a promising resource for natural product discovery and the development of a new generation of therapeutics. Unfortunately, the characterization of molecules encoded by these clusters is hampered owing to our inability to express these gene clusters in the laboratory.

Targeted metagenomics: finding rare tryptophan dimer natural products in the environment.

Natural product discovery from environmental genomes (metagenomics) has largely been limited to the screening of existing environmental DNA (eDNA) libraries. Here, we have coupled a chemical-biogeographic survey of chromopyrrolic acid synthase (CPAS) gene diversity with targeted eDNA library production to more efficiently access rare tryptophan dimer (TD) biosynthetic gene clusters. A combination of traditional and synthetic biology-based heterologous expression efforts using eDNA-derived gene clusters led to the production of hydroxysporine (1) and reductasporine (2), two bioactive TDs.

Mutations in the proteolipid subunits of the vacuolar H+-ATPase provide resistance to indolotryptoline natural products.

Indolotryptoline natural products represent a small family of structurally unique chromopyrrolic acid-derived antiproliferative agents. Like many prospective anticancer agents before them, the exploration of their potential clinical utility has been hindered by the limited information known about their mechanism of action. To study the mode of action of two closely related indolotryptolines (BE-54017, cladoniamide A), we selected for drug resistant mutants using a multidrug resistance-suppressed (MDR-sup) Schizosaccharomyces pombe strain.

Characterization of an environmental DNA-derived gene cluster that encodes the bisindolylmaleimide methylarcyriarubin.

Bisindolylmaleimides represent a naturally occurring class of metabolites that are of interest because of their protein kinase inhibition activity. From a metagenomic library constructed with soil DNA, we identified the four gene mar cluster, a bisindolylmaleimide gene cluster that encodes for methylarcyriarubin (1) production. Heterologous expression of the mar gene cluster in E.

Discovery and synthetic refactoring of tryptophan dimer gene clusters from the environment.

Here we investigate bacterial tryptophan dimer (TD) biosynthesis by probing environmental DNA (eDNA) libraries for chromopyrrolic acid (CPA) synthase genes. Functional and bioinformatics analyses of TD clusters indicate that CPA synthase gene sequences diverge in concert with the functional output of their respective clusters, making this gene a powerful tool for guiding the discovery of novel TDs from the environment. Twelve unprecedented TD biosynthetic gene clusters that can be arranged into five groups (A-E) based on their ability to generate distinct TD core substructures were recovered from eDNA libraries.

Characteristics of the first human milk bank in Taiwan.

Background: The benefits of feeding human milk to infants, even in prematurity, have been well documented. Well-organized donor milk processing has made the milk bank a good source of nutrition for premature or sick infants if their own mother's milk is not sufficient or suitable. The Taipei City Hospital Milk Bank was established in 2005 and is the first nonprofit human milk bank to operate in Taiwan.

Discovery of indolotryptoline antiproliferative agents by homology-guided metagenomic screening.

Natural product discovery by random screening of broth extracts derived from cultured bacteria often suffers from high rates of redundant isolation, making it ever more challenging to identify novel biologically interesting natural products. Here we show that homology-based screening of soil metagenomes can be used to specifically target the discovery of new members of traditionally rare, biomedically relevant natural product families. Phylogenetic analysis of oxy-tryptophan dimerization gene homologs found within a large soil DNA library enabled the identification and recovery of a unique tryptophan dimerization biosynthetic gene cluster, which we have termed the bor cluster.

Prevalence of functional gastrointestinal disorders in Taiwan: questionnaire-based survey for adults based on the Rome III criteria.

Functional gastrointestinal disorders (FGID) are a group of disorders of the digestive system in which the chronic or recurrent symptoms cannot be explained by the presence of structural or tissue abnormality. This survey used a modified Rome III questionnaire on the health and nutrition status of a general population in Taiwan during 2005-2008. A total of 4,275 responders completed the questionnaire.

Cloning and characterization of an environmental DNA-derived gene cluster that encodes the biosynthesis of the antitumor substance BE-54017.

Soil is predicted to contain thousands of unique bacterial species per gram. Soil DNA libraries represent large reservoirs of biosynthetic diversity from which diverse secondary metabolite gene clusters can be recovered and studied. The screening of an archived soil DNA library using primers designed to target oxytryptophan dimerization genes allowed us to identify and functionally characterize the first indolotryptoline biosynthetic gene cluster.

Delirium due to scopolamine patch in a 4-year-old boy.

The scopolamine patch is usually used to reduce postoperative nausea and vomiting associated with anesthesia and/or surgery. It is also commonly used for the prevention of motion sickness. Transdermal scopolamine patches have been used for decades and there are few reports in the literature of toxic psychosis associated with the product.

Cyclic vomiting syndrome in Taiwanese children.

Background/purpose: Cyclic vomiting syndrome (CVS) is a periodic and Stereotypic pattern of intractable nausea or vomiting episodes, which has been well-recognized in previous decades, although the actual pathogenesis is still unclear. Recurrent, discrete, but self-limited symptoms of nausea and vomiting bother children, and increase the cost of family and health care. This report described the clinical features of patients who fulfill the diagnostic criteria for CVS.

Expanding small-molecule functional metagenomics through parallel screening of broad-host-range cosmid environmental DNA libraries in diverse proteobacteria.

The small-molecule biosynthetic diversity encoded within the genomes of uncultured bacteria is an attractive target for the discovery of natural products using functional metagenomics. Phenotypes commonly associated with the production of small molecules, such as antibiosis, altered pigmentation, or altered colony morphology, are easily identified from screens of arrayed metagenomic library clones. However, functional metagenomic screening methods are limited by their intrinsic dependence on a heterologous expression host.

An uncommon cause of abdominal pain and diarrhea-gastrinoma in an adolescent.

Gastrinoma is a hormone-secreting tumor associated with the Zollinger-Ellison syndrome. It is quite rare among children, and it is also uncommon in locations other than the pancreas and the duodenum in the pediatric group. Here, we describe an adolescent male, presenting with recurrent secretory diarrhea and abdominal cramping pain, who had a solitary gastrinoma in the lesser sac, close to the stomach.

Natural products from environmental DNA hosted in Ralstonia metallidurans.

Metagenomic studies designed to access new small molecules from the heterologous expression of environmental DNA have focused on the use of two model systems, Escherichia coli and Streptomyces spp., as heterologous hosts. Accessing the biosynthetic potential of DNA extracted from the bacteria present in environmental samples will require the development of a more diverse collection of model bacterial hosts that can be used for screening environmental DNA libraries.

Preliminary report of transpedicle body augmenter vertebroplasty in painful vertebral tumors.

Study Design: Transpedicle body augmenter vertebroplasty of painful vertebral tumor was retrospectively evaluated.

Objective: Transpedicle body augmenter vertebroplasty was designed to treat spinal tumor with intractable pain refractory to conservative management, deformity, biomechanical impairment, and neural deficits.

Summary Of Background Data: Chemotherapy, hormonal therapy, and radiation therapy cannot restore spinal stability.