Miracle-dz/UniFAR-FTUs huggingface dataset:
Specialised tools are needed when searching the web for rare disease diagnoses

Published in: Rare Diseases DOI: 10.4161/rdis.25001 Publication date: 2013 Document version Publisher's PDF, also known as Version of record Document license: CC BY-NC Citation for published version (APA): Dragusin, R. , Petcu, P., Lioma, C. , Larsen, B. , Jørgensen, H. L. , Cox, I. , Hansen, L. K. , Ingwersen, P., & Winther, O. (2013). Specialised tools are needed when searching the web for rare disease diagnoses. Rare Diseases, 1(1), [e25001]. https://doi.org/10.4161/rdis.25001
A novel marine nitrite-oxidizing Nitrospira species from Dutch coastal North Sea water

Marine microorganisms are important for the global nitrogen cycle, but marine nitrifiers, especially aerobic nitrite oxidizers, remain largely unexplored. To increase the number of cultured representatives of marine nitrite-oxidizing bacteria (NOB), a bioreactor cultivation approach was adopted to first enrich nitrifiers and ultimately nitrite oxidizers from Dutch coastal North Sea water. With solely ammonia as the substrate an active nitrifying community consisting of novel marine Nitrosomonas aerobic ammonia oxidizers (ammonia-oxidizing bacteria) and Nitrospina and Nitrospira NOB was obtained which converted a maximum of 2 mmol of ammonia per liter per day. Switching the feed of the culture to nitrite as a sole substrate resulted in a Nitrospira NOB dominated community (approximately 80% of the total microbial community based on fluorescence in situ hybridization and metagenomic data) converting a maximum of 3 mmol of nitrite per liter per day. Phylogenetic analyses based on the 16S rRNA gene indicated that the Nitrospira enriched from the North Sea is a novel Nitrospira species with Nitrospira marina as the next taxonomically described relative (94% 16S rRNA sequence identity). Transmission electron microscopy analysis revealed a cell plan typical for Nitrospira species. The cytoplasm contained electron light particles that might represent glycogen storage. A large periplasmic space was present which was filled with electron dense particles. Nitrospira-targeted polymerase chain reaction analyses demonstrated the presence of the enriched Nitrospira species in a time series of North Sea genomic DNA samples. The availability of this new Nitrospira species enrichment culture facilitates further in-depth studies such as determination of physiological constraints, and comparison to other NOB species.
1-(4-Bromophenylsulfonyl)-2-methylnaphtho[2,1-b]furan

In the title compound, C19H13BrO3S, the 4-bromophenyl ring makes a dihedral angle of 64.11 (2)° with the mean plane [r.m.s. deviation = 0.01 (2) Å] of the naphthofuran ring. In the crystal, molecules are linked by weak C—H⋯O and C—H⋯π interactions. The crystal structure also exhibits slipped π–π interactions between the central naphthofuran benzene rings of neighbouring molecules [centroid–centroid distance = 3.559 (2), slippage = 1.036 (2) Å], and between the central naphthofuran benzene ring and the furan ring of neighbouring molecules [centroid–centroid distance = 3.655 (2), slippage = 1.136 (2) Å].
Attributable Risk Analysis Reveals Potential Healthcare Savings from Increased Consumption of Dairy Products

With rising burdens of obesity and chronic disease, the role of diet as a modifiable risk factor is of increasing public health interest. There is a growing body of evidence that low consumption of dairy products is associated with elevated risk of chronic metabolic and cardiovascular disorders. Surveys also suggest that dairy product consumption falls well below recommended targets for much of the population in many countries, including the USA, UK, and Australia. We reviewed the scientific literature on the health effects of dairy product consumption (both positive and negative) and used the best available evidence to estimate the direct healthcare expenditure and burden of disease [disability-adjusted life years (DALY)] attributable to low consumption of dairy products in Australia. We implemented a novel technique for estimating population attributable risk developed for application in nutrition and other areas in which exposure to risk is a continuous variable. We found that in the 2010–2011 financial year, AUD$2.0 billion (USD$2.1 billion, €1.6 billion, or ∼1.7% of direct healthcare expenditure) and the loss of 75,012 DALY were attributable to low dairy product consumption. In sensitivity analyses, varying core assumptions yielded corresponding estimates of AUD$1.1–3.8 billion (0.9–3.3%) and 38,299–151,061 DALY lost. The estimated healthcare cost attributable to low dairy product consumption is comparable with total spending on public health in Australia (AUD$2.0 billion in 2009–2010). These findings justify the development and evaluation of cost-effective interventions that use dairy products as a vector for reducing the costs of diet-related disease.
Ecophysiology and molecular identification of microbial populations involved in the reductive dechlorination of chloroethenes

These Ecole polytechnique federale de Lausanne EPFL, n° 2898 (2003)Section des sciences et ingenierie de l'environnementFaculte de l'environnement naturel, architectural et construitInstitut des sciences et technologies de l'environnementLaboratoire de biotechnologie environnementaleJury: Michel Aragno, Isabelle Bey, Hauke Harms, Alfons J.M. Stams Public defense: 2003-12-19 Reference doi:10.5075/epfl-thesis-2898Print copy in library catalog Record created on 2005-03-16, modified on 2016-08-08
Mss116p

RNA folding is an essential aspect underlying RNA-mediated cellular processes. Many RNAs, including large, multi-domain ribozymes, are capable of folding to the native, functional state without assistance of a protein cofactor in vitro. In the cell, trans-acting factors, such as proteins, are however known to modulate the structure and thus the fate of an RNA. DEAD-box proteins, including Mss116p, were recently found to assist folding of group I and group II introns in vitro and in vivo. The underlying mechanism(s) have been studied extensively to explore the contribution of ATP hydrolysis and duplex unwinding in helicase-stimulated intron splicing. Here we summarize the ongoing efforts to understand the novel role of DEAD-box proteins in RNA folding.
Responses to PM Exposures: Biologically Plausible Mechanisms

Low birth weight (LBW) affects 20 million infants worldwide (United Nations International Children’s Fund 2006). LBW is comprised of two overlapping etiologies: preterm delivery (PTD) and intrauterine growth retardation (IUGR). LBW, IUGR, and PTD are all significantly associated with infant mortality and an array of infant morbidities that range from pulmonary to neurologic outcomes (Martin et al. 2002). These associations form the basis for the “fetal origins” or the “Barker hypothesis” which postulates that “fetal growth retardation consequent to malnutrition has long-term structural and physiologic impacts that predisposes an individual to chronic diseases in adulthood” (Barker and Fall 1998). Perinatal outcomes are influenced by a multitude of factors including nutrition and health, genetics, physiologic stressors, and environmental toxicants such as ambient air pollution (Keen et al. 2003). In terms of the human health effects, the airborne particulate matter (PM) component has received the greatest attention (Šrám et al. 2005), and is therefore the focus for this review. Current epidemiologic evidence suggests that maternal PM exposure is correlated with several adverse perinatal outcomes (Bobak 2000; Chen et al. 2002; Dejmek et al. 2000; Salam et al. 2005; Šrám et al. 2005; Wang et al. 1997; Wilhelm and Ritz. 2005). Although these studies have become increasingly sophisticated in their measurement of PM exposures, the biologic roles of host factors that may function as effect modifiers of their relationship with birth outcomes have been less thoroughly examined. In particular, the lack of attention to nutrition factors should be considered. Nutrition can be both confounder and effect modifier of the associations between PM exposure and reproductive effects. Given the modifiable nature of both nutrition and PM exposures, future PM research and biomonitoring programs on young women would benefit greatly from the inclusion of selected nutrition factors. It is likely that women of childbearing age with nutritional risk factors (e.g., inadequate caloric intake, suboptimal protective antioxidant micronutrient status) are more likely to live in higher PM-exposed environments—confounded through their relation to socioeconomic status (SES) (Gwynn and Thurston 2001). Despite the considerable effects of nutrition among women of childbearing age, little is known about the nutrition interactions with SES and physical environment, such as PM exposure. The specific objectives of this review are threefold: to describe the biologically plausible mechanistic pathways by which PM exposure may lead to adverse perinatal outcomes (LBW, IUGR, and PTD); review the evidence showing that nutrition affects the biologic pathways; and describe biologic markers that mediate the impact of nutrition and thereby explain the mechanisms by which nutrition may serve as effect modifiers of the association between PM exposure and perinatal outcomes.
Identification of TNF-α-Responsive Promoters and Enhancers in the Intestinal Epithelial Cell Model Caco-2

The Caco-2 cell line is one of the most important in vitro models for enterocytes, and is used to study drug absorption and disease, including inflammatory bowel disease and cancer. In order to use the model optimally, it is necessary to map its functional entities. In this study, we have generated genome-wide maps of active transcription start sites (TSSs), and active enhancers in Caco-2 cells with or without tumour necrosis factor (TNF)-α stimulation to mimic an inflammatory state. We found 520 promoters that significantly changed their usage level upon TNF-α stimulation; of these, 52% are not annotated. A subset of these has the potential to confer change in protein function due to protein domain exclusion. Moreover, we locate 890 transcribed enhancer candidates, where ∼50% are changing in usage after TNF-α stimulation. These enhancers share motif enrichments with similarly responding gene promoters. As a case example, we characterize an enhancer regulating the laminin-5 γ2-chain (LAMC2) gene by nuclear factor (NF)-κB binding. This report is the first to present comprehensive TSS and enhancer maps over Caco-2 cells, and highlights many novel inflammation-specific promoters and enhancers.
Technique and Considerations in the Use of 4x1 Ring High-definition Transcranial Direct Current Stimulation (HD-tDCS)

High-definition transcranial direct current stimulation (HD-tDCS) has recently been developed as a noninvasive brain stimulation approach that increases the accuracy of current delivery to the brain by using arrays of smaller "high-definition" electrodes, instead of the larger pad-electrodes of conventional tDCS. Targeting is achieved by energizing electrodes placed in predetermined configurations. One of these is the 4x1-ring configuration. In this approach, a center ring electrode (anode or cathode) overlying the target cortical region is surrounded by four return electrodes, which help circumscribe the area of stimulation. Delivery of 4x1-ring HD-tDCS is capable of inducing significant neurophysiological and clinical effects in both healthy subjects and patients. Furthermore, its tolerability is supported by studies using intensities as high as 2.0 milliamperes for up to twenty minutes. Even though 4x1 HD-tDCS is simple to perform, correct electrode positioning is important in order to accurately stimulate target cortical regions and exert its neuromodulatory effects. The use of electrodes and hardware that have specifically been tested for HD-tDCS is critical for safety and tolerability. Given that most published studies on 4x1 HD-tDCS have targeted the primary motor cortex (M1), particularly for pain-related outcomes, the purpose of this article is to systematically describe its use for M1 stimulation, as well as the considerations to be taken for safe and effective stimulation. However, the methods outlined here can be adapted for other HD-tDCS configurations and cortical targets.
IGF 2 BP 1 A post-transcriptional “ driver ” of tumor cell migration

Commentary to: Stöhr N, Köhn M, Lederer M, Glass M, Reinke C, Singer RH, et al. IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. Genes Dev 2012; 26:176–89; PMID:22279049; http://dx.doi. org/10.1101/gad. 177642.111 The oncofetal RNA-binding protein IGF2BP1 (IGF2 mRNA binding protein 1) controls the cytoplasmic fate of specific target mRNAs including ACTB and CD44. During neural development, IGF2BPs promote neurite protrusion and the migration of neuronal crest cells. In tumor-derived cells, IGF2BP1 enhances the formation of lamellipodia and invadopodia. Accordingly, the de novo synthesis of IGF2BP1 observed in primary malignancies was reported to correlate with increased metastasis and an overall poor prognosis. However, if and how the protein enhances metastasis remains controversial. In recent studies, we reveal that IGF2BP1 promotes the directed migration of tumorderived cells in vitro by controlling the expression of MAPK4 and PTEN. The IGF2BP1-facilitated inhibition of MAPK4 mRNA translation interferes with MK5-directed phosphorylation of the heat shock protein 27 (HSP27). This limits G-actin sequestering by phosphorylated HSP27, enhances cell adhesion and elevates the velocity of tumor cell migration. Concomitantly, IGF2BP1 promotes the expression of PTEN by interfering with PTEN mRNA turnover. This results in a shift of cellular PtdIns(3,4,5)P3/ PtdIns(4,5)P2 ratios and enhances RAC1-dependent cell polarization which finally promotes the directionality of tumor cell migration. These findings identify IGF2BP1 as a potent oncogenic factor that regulates the adhesion, migration and invasiveness of tumor cells by modulating intracellular signaling. Introduction
A DNA-binding-site landscape and regulatory network analysis for NAC transcription factors in Arabidopsis thaliana

Target gene identification for transcription factors is a prerequisite for the systems wide understanding of organismal behaviour. NAM-ATAF1/2-CUC2 (NAC) transcription factors are amongst the largest transcription factor families in plants, yet limited data exist from unbiased approaches to resolve the DNA-binding preferences of individual members. Here, we present a TF-target gene identification workflow based on the integration of novel protein binding microarray data with gene expression and multi-species promoter sequence conservation to identify the DNA-binding specificities and the gene regulatory networks of 12 NAC transcription factors. Our data offer specific single-base resolution fingerprints for most TFs studied and indicate that NAC DNA-binding specificities might be predicted from their DNA-binding domain's sequence. The developed methodology, including the application of complementary functional genomics filters, makes it possible to translate, for each TF, protein binding microarray data into a set of high-quality target genes. With this approach, we confirm NAC target genes reported from independent in vivo analyses. We emphasize that candidate target gene sets together with the workflow associated with functional modules offer a strong resource to unravel the regulatory potential of NAC genes and that this workflow could be used to study other families of transcription factors.
Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery

The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders.
Phytochemical profiling, body weight effect and anti-hypercholesterolemia potentials of Cnidoscolus aconitifolius leaf extracts in male albino rat

The present study investigated the phytochemical constituents of Cnidoscolus aconitifolius leaves extracts and its anti-hypercholesterolemia potentials using standard analytical methods. Forty five male albino rats weighing (115-121 g), divided into nine groups of five rats were used. Group I served as the control while the other groups were administered 200, 400, 600 and 800 mg/kg body weight of aqueous and ethanol leaf extracts. GC-MS analysis showed 3,7,1,5-tetramethyl-2-hexadecen-1-ol, farnesyl bromide, β–sitosterol, squalene, β-amyrin, 1-heptatriacotanol, hexadecanoic acid, methyl ester, 2-pentadecanone, 6,10,14-trimethyl- ,n-hexadecanoic acid, 9,12-octadecadienoyl chloride, (Z,Z, δ- tocopherol, Ergosta-5,22-dien-3-ol acetate, (3β,22E)-, 9,10-secocholesta-5,7,10(19)-triene-3,24,25-triol, (3β,5Z,7E)-acetamide, N-methyl-N-[4-(3-hydroxypyrrolidinyl)-2-butynyl]-, 1-gala-I-ido-octose, 10-methyl-E-11-tridecen-1-ol propionate, dodecanoic acid, 2-(acetyloxy)-1-[(acetyloxy)methyl]ethyl ester, 11,14-octadecadienoic acid, methyl ester, cyclopentaneundecanoic acid and methyl ester. Lipid profile showed significant reduction in TC, LDL and TG with increase in HDL in dose dependent ratio. This shows that extracts of this plant could be useful in treatment of coronary heart diseases. Key words: Phytochemicals,hypercholesterolemia, Cnidoscolus aconitifolius, potentials.
The Anaesthetic Potency of Intrathecally Administered Levobupivacaine and Racemic Bupivacaine: A Hospital-Based Study

Background: Lower limb surgeries are often performed under spinal anesthesia. The conventional anesthetic method for lower limb surgeries is caudal epidural block. The currently available local anesthetic for this purpose is Bupivacaine which has long duration of action of around 6-12 hour. Methods: 60 adult cases ranging in age from 20 to 60 years with ASA Grade I and II requiring elective lower limb surgery under epidural anesthesia were selected for this prospective, randomized, double-blind study. Results: 60 adult cases ranging in age from 20 to 60 years with ASA Grade I and II, requiring elective gynecological surgery under epidural anesthesia were selected for this study. Cases were randomly allocated into two groups containing 20 cases each. Cases in Group B received Bupivacaine 0.25% and those in Group T received Tramadol 100mg. Conclusion: Current study concluded that both intrathecally administered levobupivacaine and racemic bupivacaine are safe and effective local anaesthetics for lower limb surgeries. Overall parameters observed in this study showed no significant difference between the two forms of the same drug. However, intrathecal levobupivacaine produces less toxicity.
Verbal and facial-emotional Stroop tasks reveal specific attentional interferences in sad mood

Mood congruence refers to the tendency of individuals to attend to information more readily when it has the same emotional content as their current mood state. The aim of the present study was to ascertain whether attentional interference occurred for participants in sad mood states for emotionally relevant stimuli (mood‐congruence), and to determine whether this interference occurred for both valenced words and valenced faces. A mood induction procedure was administered to 116 undergraduate females divided into two equal groups for the sad and happy mood condition. This study employed three versions of the Stroop task: color, verbal‐emotional, and a facial‐emotional Stroop. The two mood groups did not differ on the color Stroop. Significant group differences were found on the verbal‐emotional Stroop for sad words with longer latencies for sad‐induced participants. Main findings for the facial‐emotional Stroop were that sad mood is associated with attentional interference for angry‐threatening faces as well as longer latencies for neutral faces. Group differences were not found for positive stimuli. These findings confirm that sad mood is associated with attentional interference for mood‐congruent stimuli in the verbal domain (sad words), but this mood‐congruent effect does not necessarily apply to the visual domain (sad faces). Attentional interference for neutral faces suggests sad mood participants did not necessarily see valence‐free faces. Attentional interference for threatening stimuli is often associated with anxiety; however, the current results show that threat is not an attentional interference observed exclusively in states of anxiety but also in sad mood.
Fungal metagenomes in polyherbal medicines used for the treatment of tuberculosis

The traditional systems of medicine have significantly become more accepted in the developed and developing countries due to their curative property, less toxicity and minimal side effects. However, several studies have shown that they are associated with microbial contaminants. This study aimed at identifying fungi in nine polyherbal medicines used for the treatment of tuberculosis in Eastern Cape Province, South Africa. Sequences of fungi DNA that encodes internal transcribed spacer (ITS) region were retrieved from the remedies. The ITS region of the fungal rRNA operon was amplified using ITS1 and ITS4 primers. The amplicons were visualized on agarose gel electrophoresis, followed by end repair and adaptor ligation. They were further purified and quantified using Library Preparation kit NEBNext® UltraT DNA Library Prep Kit for illumina and run on illumina’s MiSeq platform. The study revealed that the polyherbal medicines are contaminated with fungi species. The predominant mycoflora obtained belongs to different genera or species of fungi. They include Aspergillus, Penicillium, Alternaria, Candida, Ramularia, Cladosporium and Malassezia among others. Some of these organisms are capable of causing infections in immunocompromised patients. Thus, the study identified various fungal contaminants in polyherbal remedies sold to tuberculosis patients in five communities in the Eastern Cape Province of South Africa. Key words: Fungi, internal transcribed spacer (ITS) region, polyherbal medicines, public health, tuberculosis.