bZIPDB : A database of regulatory information for human bZIP transcription factors

<p>Abstract</p> <p>Background</p> <p>Basic region-leucine zipper (bZIP) proteins are a class of transcription factors (TFs) that play diverse roles in eukaryotes. Malfunctions in these proteins lead to cancer and various other diseases. For detailed characterization of these TFs, further public resources are required.</p> <p>Description</p> <p>We constructed a database, designated bZIPDB, containing information on 49 human bZIP TFs, by means of automated literature collection and manual curation. bZIPDB aims to provide public data required for deciphering the gene regulatory network of the human bZIP family, e.g., evaluation or reference information for the identification of regulatory modules. The resources provided by bZIPDB include (1) protein interaction data including direct binding, phosphorylation and functional associations between bZIP TFs and other cellular proteins, along with other types of interactions, (2) bZIP TF-target gene relationships, (3) the cellular network of bZIP TFs in particular cell lines, and (4) gene information and ontology. In the current version of the database, 721 protein interactions and 560 TF-target gene relationships are recorded. bZIPDB is annually updated for the newly discovered information.</p> <p>Conclusion</p> <p>bZIPDB is a repository of detailed regulatory information for human bZIP TFs that is collected and processed from the literature, designed to facilitate analysis of this protein family. bZIPDB is available for public use at <url>http://biosoft.kaist.ac.kr/bzipdb</url>.</p

An Epigenetic Signature for Within-Generational Plasticity of a Reef Fish to Ocean Warming

Elevated temperature can have detrimental effects on the physiological performance of many marine organisms. However, phenotypic plasticity may enable some populations to maintain their performance under thermal stress. Two longitudinally separated populations of the coral reef fish, Acanthochromis polyacanthus from the Great Barrier Reef have shown differing capacities for thermal plasticity - the southernmost Heron Island population restored aerobic scope within one generation at a higher temperature, whereas the northernmost Palm Island population restored aerobic scope only when two generations were exposed to warmer conditions. We recently discovered an epigenetic signature associated with transgenerational plasticity in the Palm Island population. Here, we aimed to determine if epigenetic changes are also associated with the within-generational plasticity observed in the Heron Island population and, if so, how this epigenetic signature compares to the Palm Island transgenerational epigenome. By sequencing and analyzing the genome-wide DNA methylome of fish reared at control (+0 degrees C) or elevated temperatures (+1.5 and +3 degrees C) since early life, we identified 480 differentially methylated genomic regions and 372 adjacent protein-coding genes associated with within-generational plasticity in the Heron Island population. Functions related to insulin, cardiovascular capacity, development, and heat response were significantly enriched in differentially methylated genes, suggesting that these functions are the core mechanisms for within-generational restoration of aerobic scope. Comparison to the differentially methylated genes identified from F2 Palm Island population revealed little overlap of genes and enriched functions, indicating that distinct genetic toolkits may be used for within- and between-generational plasticity to ocean warming in the same species from different latitudes

Myeloid-Derived Suppressor Cells Are Controlled by Regulatory T Cells via TGF-β during Murine Colitis

Myeloid-derived suppressor cells (MDSCs) are well known regulators of regulatory T cells (Treg cells); however, the direct regulation of MDSCs by Treg cells has not been well characterized. We find that colitis caused by functional deficiency of Treg cells leads to altered expansion and reduced function of MDSCs. During differentiation of MDSCs in vitro from bone marrow cells, Treg cells enhanced MDSC function and controlled their differentiation through a mechanism involving transforming growth factor-β (TGF-β). TGF-β-deficient Treg cells were not able to regulate MDSC function in an experimentally induced model of colitis. Finally, we evaluated the therapeutic effect of TGF-β-mediated in-vitro-differentiated MDSCs on colitis. Adoptive transfer of MDSCs that differentiated with TGF-β led to better colitis prevention than the transfer of MDSCs that differentiated without TGF-β. Our results demonstrate an interaction between Treg cells and MDSCs that contributes to the regulation of MDSC proliferation and the acquisition of immunosuppressive functions

Magnetic Resonance Imaging Features of Normal Thyroid Parenchyma and Incidental Diffuse Thyroid Disease: A Single-Center Study

Background: No previous studies have investigated the feasibility of magnetic resonance imaging (MRI) diagnosis for detecting incidental diffuse thyroid disease (DTD). This study investigated MRI features of normal thyroid parenchyma and incidental DTD.Methods: From January 2008 to December 2017, 387 patients underwent neck MRI in our hospital due to tumor/nodal staging (n = 137), lymphadenopathy (n = 122), inflammatory neck lesion (n = 85), congenital neck lesion (n = 12), and patient request (n = 31). Among them, 375 patients were excluded because of a lack of appropriate histopathological data on the thyroid parenchyma.Results: Among the patients included, 10 had normal thyroid parenchyma, 1 had Hashimoto thyroiditis, and 1 had diffuse hyperplasia. The common MRI features of normal thyroid parenchyma include iso-/slightly high and homogeneous signal intensity on T1/T2-weighted images, normal anteroposterior diameter of the thyroid gland, smooth margin, and homogeneously increased enhancement as compared to adjacent muscle. Hashimoto thyroiditis exhibited high and inhomogeneous signal intensity on T2-weighted images, while diffuse hyperplasia revealed an increased anteroposterior diameter and lobulated margin of the thyroid gland, and inhomogeneous enhancement.Conclusions: MRI may be helpful for detection of incidental DTD

Comparison of Postoperative Neck Pain and Discomfort, Swallowing Difficulty, and Voice Change After Conventional Open, Endoscopic, and Robotic Thyroidectomy: A Single-Center Cohort Study

Background: The objective of this study was to compare the postoperative neck pain and discomfort, swallowing difficulty, and voice change after conventional open thyroidectomy (COT), endoscopic thyroidectomy (ET), or robotic thyroidectomy (RT) performed by a single surgeon.Methods: From January 2013 to December 2017, 254 patients underwent COT, ET, or RT performed by a single surgeon and completed a postoperative symptom survey conducted in the outpatient clinic by three nurses. The survey collected information on postoperative neck pain and discomfort, swallowing difficulty, and voice change.Results: Of the 254 patients, 169 underwent COT, 32 underwent ET, and 53 underwent RT. The mean age in the COT, ET, and RT groups was 50.1, 44.5, and 41.6 years, respectively. The mean interval between thyroidectomy and survey in the COT, ET, and RT groups was 42.7, 50.2, and 9.2 months, respectively. Postoperative neck pain was significantly higher in the ET and RT groups than in the COT group (p = 0.026). The average neck impairment index score in the RT group was significantly higher than that in the COT group (p &lt; 0.001). There were no significant differences in pain scale scores, swallowing difficulty, swallowing impairment index, voice change, and voice hand index among the three groups.Conclusions: There were no significant differences in postoperative voice change or swallowing difficulty among the COT, ET, and RT groups, whereas neck pain and discomfort were more common after ET and RT than COT

The Draft Genome of an Octocoral, Dendronephthya gigantea

Coral reefs composed of stony corals are threatened by global marine environmental changes. However, soft coral communities of octocorallian species, appear more resilient. The genomes of several cnidarians species have been published, including from stony corals, sea anemones, and hydra. To fill the phylogenetic gap for octocoral species of cnidarians, we sequenced the octocoral, Dendronephthya gigantea, a nonsymbiotic soft coral, commonly known as the carnation coral. The D. gigantea genome size is similar to 276 Mb. A high-quality genome assembly was constructed from PacBio long reads (29.85 Gb with 108x coverage) and Illumina short paired-end reads (35.54 Gb with 128x coverage) resulting in the highest N50 value (1.4 Mb) reported thus far among cnidarian genomes. About 12% of the genome is repetitive elements and contained 28,879 predicted protein-coding genes. This gene set is composed of 94% complete BUSCO ortholog benchmark genes, which is the second highest value among the cnidarians, indicating high quality. Based on molecular phylogenetic analysis, octocoral and hexacoral divergence times were estimated at 544 MYA. There is a clear difference in Hox gene composition between these species: unlike hexacorals, the Antp superclass Evx gene was absent in D. gigantea. Here, we present the first genome assembly of a nonsymbiotic octocoral, D. gigantea to aid in the comparative genomic analysis of cnidarians, including stony and soft corals, both symbiotic and nonsymbiotic. The D. gigantea genome may also provide clues to mechanisms of differential coping between the soft and stony corals in response to scenarios of global warming

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration ClinicalTrials.gov Identifier NCT0158936