snu-aidas/HVMap-dataset huggingface dataset:
Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila.

The Drosophila gene eyeless (ey) encodes a transcription factor with both a paired domain and a homeodomain. It is homologous to the mouse Small eye (Pax-6) gene and to the Aniridia gene in humans. These genes share extensive sequence identity, the position of three intron splice sites is conserved, and these genes are expressed similarly in the developing nervous system and in the eye during morphogenesis. Loss-of-function mutations in both the insect and in the mammalian genes have been shown to lead to a reduction or absence of eye structures, which suggests that ey functions in eye morphogenesis. By targeted expression of the ey complementary DNA in various imaginal disc primordia of Drosophila, ectopic eye structures were induced on the wings, the legs, and on the antennae. The ectopic eyes appeared morphologically normal and consisted of groups of fully differentiated ommatidia with a complete set of photoreceptor cells. These results support the proposition that ey is the master control gene for eye morphogenesis. Because homologous genes are present in vertebrates, ascidians, insects, cephalopods, and nemerteans, ey may function as a master control gene throughout the metazoa.
Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer

To identify new genetic factors for colorectal cancer (CRC), we conducted a                 genome-wide association study in east Asians. By analyzing genome-wide data in 2,098                 cases and 5,749 controls, we selected 64 promising SNPs for replication in an                 independent set of samples, including up to 5,358 cases and 5,922 controls. We                 identified four SNPs with association P values of 8.58 ×                     10(-7) to 3.77 × 10(-10)                 in the combined analysis of all east Asian samples. Three of the four were                 replicated in a study conducted in 26,060 individuals of European descent, with                 combined P values of 1.22 × 10(-10) for                 rs647161 (5q31.1), 6.64 × 10(-9) for rs2423279                 (20p12.3) and 3.06 × 10(-8) for rs10774214                 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both                 east Asian and European-ancestry populations. This study identified three new CRC                 susceptibility loci and provides additional insight into the genetics and biology of                 CRC.
Long non-coding RNAs as novel players in β cell function and type 1 diabetes

BACKGROUND Long non-coding RNAs (lncRNAs) are a sub-class within non-coding RNA repertoire that have emerged as crucial regulators of the gene expression in various pathophysiological conditions. lncRNAs display remarkable versatility and wield their functions through interactions with RNA, DNA, or proteins. Accumulating body of evidence based on multitude studies has highlighted the role of lncRNAs in many autoimmune and inflammatory diseases, including type 1 diabetes (T1D). This review highlights emerging roles of lncRNAs in immune and islet β cell function as well as some of the challenges and opportunities in understanding the pathogenesis of T1D and its complications. CONCLUSION We accentuate that the lncRNAs within T1D-loci regions in consort with regulatory variants and enhancer clusters orchestrate the chromatin remodeling in β cells and thereby act as cis/trans-regulatory determinants of islet cell transcriptional programs.
Costs of the COPD. Differences between intensive care unit and respiratory intermediate care unit.

INTRODUCTION To assess whether respiratory intermediate care units (RICUs) are cost effective alternatives to intensive care units (ICUs) for patients with exacerbation of chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS Multi-centre, prospective, bottom-up cost study performed in 15 ICUs and 6 RICUs. COPD patients staying longer than 48 h were recruited; those coming from other ICUs/RICUs, with immune-deficiency or stroke, were excluded. After the ICU sample was standardised to the RICU distribution of the reason-for-admission and infusion of a vasoactive drug on admission, 60 ICU patients and 65 RICU patients remained, of the original 164 recruited. For each patient, besides clinical data on admission and discharge, daily information about the resources consumed were recorded and analysed in terms of their costs. RESULTS Total cost per patient was lower in RICUs than in ICUs (754 vs. 1507 Euro; P < 0.0001). In all items, except drugs and nutrition, we found a significant lower cost in RICUs. Dead patients were noticeably different in terms of disease severity between ICUs and RICUs, while surviving ones were not. CONCLUSIONS Our study suggests that some COPD patients, less severe and with pure respiratory failure, could be successfully and less costly treated in RICUs.
in polyploid species

We developed the Yeast Gene Order Browser (YGOB; http://wolfe.gen.tcd.ie/ygob) to facilitate visual comparisons and computational analysis of synteny relationships in yeasts. The data presented in YGOB, currently covering seven species, are based on sets of homologous genes that have been intensively manually curated based on both sequence similarity and genomic context (synteny). We reconciled different laboratories' lists of paralogous Saccharomyces cerevisiae gene pairs formed by genome duplication (ohnologs), and present near-exhaustive lists of the ohnolog pairs retained in S. cerevisiae (551, including 22 previously unidentified), Saccharomyces castellii (599), and Candida glabrata (404).
Immune complex relay by subcapsular sinus macrophages and non-cognate B cells drives antibody affinity maturation

Subcapsular sinus (SCS) macrophages capture antigens from lymph and present them intact for B cell encounter and follicular delivery. However, the properties of SCS macrophages are poorly defined. Here we show SCS macrophage development depended on lymphotoxin-alpha1beta2, and the cells had low lysosomal enzyme expression and retained opsonized antigens on their surface. Intravital imaging revealed immune complexes moving along macrophage processes into the follicle. Moreover, noncognate B cells relayed antigen opsonized by newly produced antibodies from the subcapsular region to the germinal center, and affinity maturation was impaired when this transport process was disrupted. Thus, we characterize SCS macrophages as specialized antigen-presenting cells functioning at the apex of an antigen transport chain that promotes humoral immunity.
Promoter decoding of transcription factor dynamics involves a trade-off between noise and control of gene expression

Numerous transcription factors (TFs) encode information about upstream signals in the dynamics of their activation, but how downstream genes decode these dynamics remains poorly understood. Using microfluidics to control the nucleocytoplasmic translocation dynamics of the budding yeast TF Msn2, we elucidate the principles that govern how different promoters convert dynamical Msn2 input into gene expression output in single cells. Combining modeling and experiments, we classify promoters according to their signal-processing behavior and reveal that multiple, distinct gene expression programs can be encoded in the dynamics of Msn2. We show that both oscillatory TF dynamics and slow promoter kinetics lead to higher noise in gene expression. Furthermore, we show that the promoter activation timescale is related to nucleosome remodeling. Our findings imply a fundamental trade-off: although the cell can exploit different promoter classes to differentially control gene expression using TF dynamics, gene expression noise fundamentally limits how much information can be encoded in the dynamics of a single TF and reliably decoded by promoters.
GaAs nanopillar-array solar cells employing in situ surface passivation

Arrays of III-V direct-bandgap semiconductor nanopillars represent promising photovoltaic candidates due to their inherent high optical absorption coefficients and minimized reflection arising from light trapping, efficient charge collection in the radial direction and the ability to synthesize them on low-cost platforms. However, the increased surface area results in surface states that hamper the power conversion efficiency. Here, we report the first demonstration of GaAs nanopillar-array photovoltaics employing epitaxial passivation with air mass 1.5 global power conversion efficiencies of 6.63%. High-bandgap epitaxial InGaP shells are grown in situ and cap the radial p-n junctions to alleviate surface-state effects. Under light, the photovoltaic devices exhibit open-circuit voltages of 0.44 V, short-circuit current densities of 24.3 mA cm(-2) and fill factors of 62% with high external quantum efficiencies >70% across the spectral regime of interest. A novel titanium/indium tin oxide annealed alloy is exploited as transparent ohmic anode.
The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.
Radioiodine treatment of multinodular non-toxic goitre.

OBJECTIVE To investigate the long term effect of radioactive iodine on thyroid function and size in patients with non-toxic multinodular goitre. DESIGN Consecutive patients with multinodular non-toxic goitre selected for radioactive iodine treatment and followed for a minimum of 12 months (median 48 months) after an intended dose of 3.7 MBq/g thyroid tissue corrected to a 100% uptake of iodine-131 in 24 hours. PATIENTS 69 patients with a growing multinodular non-toxic goitre causing local compression symptoms or cosmetic inconveniences. The treatment was chosen because of a high operative risk, previous thyroidectomy, or refusal to be operated on. MAIN OUTCOME MEASUREMENTS Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 1, 2, 3, 6, and 12 months after treatment and then once a year. RESULTS 56 patients were treated with a single dose of 131I, 12 with two doses, and one with four doses. In 45 patients treated with one dose and remaining euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (23-48) ml at 24 months in the 39 patients in whom this was measured during follow up. The median reduction was 40 (22-48) ml (60% reduction, p < 0.0001), half of which occurred within three months. Patients treated with two doses as well as those developing hypothyroidism and hyperthyroidism had a significant reduction in thyroid volume. Eleven patients developed hypothyroidism (cumulative five year risk 22%, 95% confidence interval 4.8% to 38.4%). Side effects were few: three cases of hyperthyroidism and two cases of radiation thyroiditis. Only one patient was dissatisfied with the result; she was referred for operation six months after treatment. CONCLUSIONS A substantial reduction in thyroid volume accompanied by a low incidence of hypothyroidism and few side effects makes the use of radioactive iodine an attractive alternative to surgery in selected cases of non-toxic multinodular goitre.
Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia

Neurodegenerative diseases, such as frontotemporal dementia (FTD), are often associated with behavioral deficits, but the underlying anatomical and molecular causes remain poorly understood. Here we show that forebrain-specific expression of FTD-associated mutant CHMP2B in mice causes several age-dependent neurodegenerative phenotypes, including social behavioral impairments. The social deficits were accompanied by a change in AMPA receptor (AMPAR) composition, leading to an imbalance between Ca(2+)-permeable and Ca(2+)-impermeable AMPARs. Expression of most AMPAR subunits was regulated by the brain-enriched microRNA miR-124, whose abundance was markedly decreased in the superficial layers of the cerebral cortex of mice expressing the mutant CHMP2B. We found similar changes in miR-124 and AMPAR levels in the frontal cortex and induced pluripotent stem cell-derived neurons from subjects with behavioral variant FTD. Moreover, ectopic miR-124 expression in the medial prefrontal cortex of mutant mice decreased AMPAR levels and partially rescued behavioral deficits. Knockdown of the AMPAR subunit Gria2 also alleviated social impairments. Our results identify a previously undescribed mechanism involving miR-124 and AMPARs in regulating social behavior in FTD and suggest a potential therapeutic avenue.
Activated AMPK boosts the Nrf2/HO-1 signaling axis—A role for the unfolded protein response

In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regulators of the cellular redox and energy balance, respectively. Making use of xanthohumol (XN) as an activator of both the AMPK and the Nrf2 signaling pathway we show that AMPK exerts a positive influence on Nrf2/heme oxygenase (HO)-1 signaling in mouse embryonic fibroblasts. Genetic ablation and pharmacological inhibition of AMPK blunts Nrf2-dependent HO-1 expression by XN already at the mRNA level. XN leads to AMPK activation via interference with mitochondrial function and activation of liver kinase B1 as upstream AMPK kinase. The subsequent AMPK-mediated enhancement of the Nrf2/HO-1 response does not depend on inhibition of the mammalian target of rapamycin, inhibition of glycogen synthase kinase 3β, or altered abundance of Nrf2 (total and nuclear). However, reduced endoplasmic reticulum stress was identified and elaborated as a step in the AMPK-augmented Nrf2/HO-1 response. Overall, we shed more light on the hitherto incompletely understood cross talk between the LKB1/AMPK and the Nrf2/HO-1 axis revealing for the first time involvement of the unfolded protein response as an additional player and suggesting tight cooperation between signaling pathways controlling cellular redox, energy, or protein homeostasis.
The IDEAL recommendations and urological innovation

Like other branches of surgery, Urology has encountered major challenges in aligning the research processes by which new interventions are assessed with the principles of Evidence-Based Medicine. This article explains the IDEAL framework and recommendations and illustrates how they might affect the evaluation of current controversial urological procedures. From an inside perspective, we provide an overview of the efforts of the IDEAL Working Group to date with special emphasis on the field of Urology. There are clear differences between drugs and interventions in the natural history of innovations. Since the conventional framework for conducting trials of new treatments is largely based on the former, the evaluation of surgical innovations using the same template can encounter significant problems. Difficulties in performing randomized controlled trials of surgical techniques and the persistence of the case series as an important feature of the scientific literature have been the two most controversial aspects of this mismatch between the subject of research and the methodology used. The IDEAL framework provides a description of the process of innovation and development for surgical trials, and the associated recommendations provide a suggested alternative approach to developing study designs, which are appropriate for the specific problems of new techniques. IDEAL provides a new framework for surgical innovation that was developed with broad stakeholder input from the surgical community and is expected to have a transformative impact on the way that urologists perform clinical research.
Prolonged conservative care versus early surgery in patients with sciatica caused by lumbar disc herniation: two year results of a randomised controlled trial.

OBJECTIVES To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up. DESIGN Randomised controlled trial. SETTING Nine Dutch hospitals. PARTICIPANTS 283 patients with 6-12 weeks of sciatica. INTERVENTIONS Early surgery or an intended six months of continued conservative treatment, with delayed surgery if needed. MAIN OUTCOME MEASURES Scores from Roland disability questionnaire for sciatica, visual analogue scale for leg pain, and Likert self rating scale of global perceived recovery. RESULTS Of the 141 patients assigned to undergo early surgery, 125 (89%) underwent microdiscectomy. Of the 142 patients assigned to conservative treatment, 62 (44%) eventually required surgery, seven doing so in the second year of follow-up. There was no significant overall difference between treatment arms in disability scores during the first two years (P=0.25). Improvement in leg pain was faster for patients randomised to early surgery, with a significant difference between "areas under the curves" over two years (P=0.05). This short term benefit of early surgery was no longer significant by six months and continued to narrow between six months and 24 months. Patient satisfaction decreased slightly between one and two years for both groups. At two years 20% of all patients reported an unsatisfactory outcome. CONCLUSIONS Early surgery achieved more rapid relief of sciatica than conservative care, but outcomes were similar by one year and these did not change during the second year. TRIAL REGISTRY ISRCT No 26872154.
IGF2 is parentally imprinted during human embryogenesis and in the Beckwith–Wiedemann syndrome

The phenomenon of parental imprinting involves the preferential expression of one parental allele of a subset of chromosomal genes and has so far only been documented in the mouse. We show here, by exploiting sequence polymorphisms in exon nine of the human insulin–like growth factor 2 (IGF2) gene, that only the paternally–inherited allele is active in embryonic and extra–embryonic cells from first trimester pregnancies. In addition, only the paternal allele is expressed in tissues from a patient who suffered from Beckwith–Wiedemann syndrome. Thus the parental imprinting of IGF2 appears to be evolutionarily conserved from mouse to man and has implications for the generation of the Beckwith–Wiedemann syndrome.
Safety and reliability of Radio Frequency Identification Devices in Magnetic Resonance Imaging and Computed Tomography

BACKGROUND Radio Frequency Identification (RFID) devices are becoming more and more essential for patient safety in hospitals. The purpose of this study was to determine patient safety, data reliability and signal loss wearing on skin RFID devices during magnetic resonance imaging (MRI) and computed tomography (CT) scanning. METHODS Sixty RFID tags of the type I-Code SLI, 13.56 MHz, ISO 18000-3.1 were tested: Thirty type 1, an RFID tag with a 76 x 45 mm aluminum-etched antenna and 30 type 2, a tag with a 31 x 14 mm copper-etched antenna. The signal loss, material movement and heat tests were performed in a 1.5 T and a 3 T MR system. For data integrity, the tags were tested additionally during CT scanning. Standardized function tests were performed with all transponders before and after all imaging studies. RESULTS There was no memory loss or data alteration in the RFID tags after MRI and CT scanning. Concerning heating (a maximum of 3.6 degrees C) and device movement (below 1 N/kg) no relevant influence was found. Concerning signal loss (artifacts 2 - 4 mm), interpretability of MR images was impaired when superficial structures such as skin, subcutaneous tissues or tendons were assessed. CONCLUSIONS Patients wearing RFID wristbands are safe in 1.5 T and 3 T MR scanners using normal operation mode for RF-field. The findings are specific to the RFID tags that underwent testing.
Alterations on peripheral B cell subsets following an acute uncomplicated clinical malaria infection in children

BACKGROUND The effects of Plasmodium falciparum on B-cell homeostasis have not been well characterized. This study investigated whether an episode of acute malaria in young children results in changes in the peripheral B cell phenotype. METHODS Using flow-cytofluorimetric analysis, the B cell phenotypes found in the peripheral blood of children aged 2-5 years were characterized during an episode of acute uncomplicated clinical malaria and four weeks post-recovery and in healthy age-matched controls. RESULTS There was a significant decrease in CD19+ B lymphocytes during acute malaria. Characterization of the CD19+ B cell subsets in the peripheral blood based on expression of IgD and CD38 revealed a significant decrease in the numbers of naive 1 CD38-IgD+ B cells while there was an increase in CD38+IgD- memory 3 B cells during acute malaria. Further analysis of the peripheral B cell phenotype also identified an expansion of transitional CD10+CD19+ B cells in children following an episode of acute malaria with up to 25% of total CD19+ B cell pool residing in this subset. CONCLUSION Children experiencing an episode of acute uncomplicated clinical malaria experienced profound disturbances in B cell homeostasis.
SETD2: an epigenetic modifier with tumor suppressor functionality

In the past decade important progress has been made in our understanding of the epigenetic regulatory machinery. It has become clear that genetic aberrations in multiple epigenetic modifier proteins are associated with various types of cancer. Moreover, targeting the epigenome has emerged as a novel tool to treat cancer patients. Recently, the first drugs have been reported that specifically target SETD2-negative tumors. In this review we discuss the studies on the associated protein, Set domain containing 2 (SETD2), a histone modifier for which mutations have only recently been associated with cancer development. Our review starts with the structural characteristics of SETD2 and extends to its corresponding function by combining studies on SETD2 function in yeast, Drosophila, Caenorhabditis elegans, mice, and humans. SETD2 is now generally known as the single human gene responsible for trimethylation of lysine 36 of Histone H3 (H3K36). H3K36me3 readers that recruit protein complexes to carry out specific processes, including transcription elongation, RNA processing, and DNA repair, determine the impact of this histone modification. Finally, we describe the prevalence of SETD2-inactivating mutations in cancer, with the highest frequency in clear cell Renal Cell Cancer, and explore how SETD2-inactivation might contribute to tumor development.