julilili42/papers huggingface dataset:
Antibiotic Selection Pressure Determination through Sequence-Based Metagenomics
2015-09-15

ABSTRACT The human gut forms a dynamic reservoir of antibiotic resistance genes (ARGs). Treatment with antimicrobial agents has a significant impact on the intestinal resistome and leads to enhanced horizontal transfer and selection of resistance. We have monitored the development of intestinal ARGs over a 6-day course of ciprofloxacin (Cp) treatment in two healthy individuals by using sequenced-based metagenomics and different ARG quantification methods. Fixed- and random-effect models were applied to determine the change in ARG abundance per defined daily dose of Cp as an expression of the respective selection pressure. Among various shifts in the composition of the intestinal resistome, we found in one individual a strong positive selection for class D beta-lactamases which were partly located on a mobile genetic element. Furthermore, a trend to a negative selection has been observed with class A beta-lactamases (−2.66 hits per million sample reads/defined daily dose; P = 0.06). By 4 weeks after the end of treatment, the composition of ARGs returned toward their initial state but to a different degree in both subjects. We present here a novel analysis algorithm for the determination of antibiotic selection pressure which can be applied in clinical settings to compare therapeutic regimens regarding their effect on the intestinal resistome. This information is of critical importance for clinicians to choose antimicrobial agents with a low selective force on their patients' intestinal ARGs, likely resulting in a diminished spread of resistance and a reduced burden of hospital-acquired infections with multidrug-resistant pathogens.
Current Strategies in the Treatment of Scars and Keloids
2015-09-15

Hypertrophic scars (HTSs) and keloids are a major health concern for aesthetic and functional reasons. Despite a plethora of rapidly evolving treatment options and technical advances, the management of pathologic scarring remains difficult. The development of standardized treatment algorithms has been problematic for years due to the lack of sound randomized controlled trials. Expert panels are more and more establishing guidelines to provide an evidence-based framework on a national and international level. This article aims to evaluate the current strategies and upcoming trends in the therapy and prevention of unpleasant scars and keloids from a clinical perspective. There is strong evidence to support a growing role of early combination treatments, particularly the application of 5-fluoruracil adjunct to intralesional steroid injections. Furthermore, the use of fractional ablative laser technologies such as the CO2 laser has recently yielded promising results with respect to aesthetic outcomes and patient satisfaction at tolerable side effects.
Bevacizumab treatment for symptomatic spinal ependymomas in neurofibromatosis type 2
2015-09-15

Treatment using bevacizumab improved symptoms related to NF2-associated ependymomas, often without concurrent radiographic response. This treatment effect may be related to VEGF-R1 expression in NF2-associated ependymoma.
A molecular phylogenetic framework for Anthracocystis (Ustilaginales), including five new combinations (inter alia for the asexual Pseudozyma flocculosa), and description of Anthracocystis grodzinskae sp. nov.
2015-09-15

The genus Anthracocystis (Ustilaginales, Ustilaginaceae) was recently reinstated for grass-infecting species of smut fungi that have sori with a peridium composed of mostly fungal cells, filiform or slender columellae, persistent spore balls usually composed of dimorphic spores, and lacking sterile cells between spore balls. In this study, Anthracocystis grodzinskae sp. nov. on Euclasta condylotricha is described and illustrated from the Sudanian savanna biome in Benin (West Africa). The new species is compared with two other smut fungi known on Euclasta condylotricha, namely Sporisorium euclastae and Anthracocystis ischaemoides, in Zambia. It differs from these species in a number of morphological characters that are discussed in detail. The systematic position of A. grodzinskae was investigated in a phylogenetic analysis with a concatenated supermatrix of the internal transcribed spacer (ITS) and large subunit (LSU) regions of ribosomal DNA. The dataset included all representatives of Anthracocystis for which sequences were available in the National Center for Biotechnology Information's (NCBI's) GenBank and that were linked to reliably identified source specimens, related yeast species, and unnamed yeast strains or environmental sequences. The phylogenetic hypothesis derived from the dataset is intended to serve as a backbone tree for Anthracocystis. 19 ITS and 13 LSU sequences were tracked to represent sequences generated from type specimens (holotypes, isotypes or paratypes). These type sequences are recommended to be deposited in the RefSeq Targeted Loci database. This study provides the first explicit evidence that several asexual species are nested within the Anthracocystis lineage. The yeast sequences were scattered in different subclades of Anthracocystis and none of them could be directly assigned to a teleomorphic species. Only one of these yeast anamorphs was assigned to a species, namely Pseudozyma flocculosa. In line with the current code of nomenclature, and following recent practice of merging yeast species with sexual species under the older generic name, this yeast is recombined into Anthracocystis as A. flocculosa. Additionally, new combinations are proposed for four teliosporic species (Anthracocystis andrewmitchellii, A. christineae, A. kenyana, A. warambiensis).
Prognostic impact of circulating Her-2-reactive T-cells producing pro- and/or anti-inflammatory cytokines in elderly breast cancer patients
2015-09-15

Elderly breast cancer patients appear perfectly immunocompetent to respond to Her-2 peptide pools in vitro, with response patterns very similar to younger patients. The nature of this response is associated with 5-year survival of these elderly patients, suggesting that boosting anti-tumor responses and modulating the nature of the T-cell response is likely to be effective even in potentially immunosenescent elderly breast cancer patients, and might be useful for predicting which patients are most likely to benefit from such treatments.
Phosphorylation Affects DNA-Binding of the Senescence-Regulating bZIP Transcription Factor GBF1
2015-09-16

Massive changes in the transcriptome of Arabidopsis thaliana during onset and progression of leaf senescence imply a central role for transcription factors. While many transcription factors are themselves up- or down-regulated during senescence, the bZIP transcription factor G-box-binding factor 1 (GBF1/bZIP41) is constitutively expressed in Arabidopsis leaf tissue but at the same time triggers the onset of leaf senescence, suggesting posttranscriptional mechanisms for senescence-specific GBF1 activation. Here we show that GBF1 is phosphorylated by the threonine/serine CASEIN KINASE II (CKII) in vitro and that CKII phosphorylation had a negative effect on GBF1 DNA-binding to G-boxes of two direct target genes, CATALASE2 and RBSCS1a. Phosphorylation mimicry at three serine positions in the basic region of GBF1 also had a negative effect on DNA-binding. Kinase assays revealed that CKII phosphorylates at least one serine in the basic domain but has additional phosphorylation sites outside this domain. Two different ckII α subunit1 and one α subunit2 T-DNA insertion lines showed no visible senescence phenotype, but in all lines the expression of the senescence marker gene SAG12 was remarkably diminished. A model is presented suggesting that senescence-specific GBF1 activation might be achieved by lowering the phosphorylation of GBF1 by CKII.
Bifurcation of the quasinormal spectrum and zero damped modes for rotating dilatonic black holes
2015-09-16

It has been recently found that for the near extremal Kerr black holes\\nappearing of Zero Damped Modes (accompanied by qusinormal mode branching)\\nsignifies about inapplicability of the regime of small perturbations and the\\nonset of turbulence. Here we show that this phenomena is not limited by Kerr or\\nKerr-Newman solutions only, but also takes place for rotating dilatonic black\\nholes for which we have found Zero Damped Modes both numerically and\\nanalytically. We have also shown that, contrary to recent claims, there is no\\ninstability of a charged massive scalar field in the background of the rotating\\ndilatonic black hole under physically adequate boundary conditions. Analytic\\nexpression for dominant quasinormal frequencies is deduced in the regime of\\nlarge coupling qQ, where q and Q are the field and black hole charges\\nrespectively.\\n
Making “Friends” in a Virtual World
2015-09-16

Graphical virtual worlds add two new layers to the old question what determines friendship formation. First, it is possible to distinguish between off-line (player) and online (avatar) characteristics. Second, these environments offer new possibilities for studying friendship formation. By tracking friendship requests and their acceptance rate, researchers are able to distinguish between with whom players want to become friends and with whom they actually do become friends. This article examined friendship formation in Timik, a graphical virtual world targeted at Polish teenagers. Homophily, preferential attachment and status were tested as possible underlying mechanisms. Results showed that preferential attachment and status drove invitations: Players wanted to become friends with high-status players. However, high-status players were also more likely to reject offers. Homophily only played a minor role. Players preferred players of the same avatar class and similar age but of the opposite sex. Too similar avatars were disliked. The results are discussed in the light of the generalizability of off-line theories of friendship formation to online worlds.
Considerations for orthotopic diversions in women
2015-09-16

Surgical meticulousness, but not the technique itself, is important for improved functional outcomes of patients with urinary diversion. Novel surgical techniques need to concentrate around the question of how to improve surgical meticulousness during the preparation of critical anatomical structures at radical pelvic surgery.
Proinflammatory mesenchymal effects of the non-genotoxic hepatocarcinogen phenobarbital: a novel mechanism of antiapoptosis and tumor promotion
2015-09-16

Many environmental pollutants and drugs, including steroid hormones, hypolipidemics and antiepileptics, are non-genotoxic carcinogens (NGC) in rodent liver. The mechanism of action and the risk for human health are still insufficiently known. Here, we study the effects of phenobarbital (PB), a widely used model NGC, on hepatic epithelial-mesenchymal crosstalk and the impact on hepatic apoptosis. Mesenchymal cells (MC) and hepatocytes (HC) were isolated from control and PB-treated rat livers. PB induced extensive changes in gene expression in MC and much less in HC as shown by transcriptomics with oligoarrays. In MC only, transcript levels of numerous proinflammatory cytokines were elevated. Correspondingly, ELISA on the supernatant of MC from PB-treated rats revealed enhanced release of various cytokines. In cultured HC, this supernatant caused (i) nuclear translocation and activation of nuclear factor-κB (shown by immunoblots of nuclear extracts and reporter gene assays), (ii) elevated expression of proinflammatory genes and (iii) protection from the proapoptotic action of transforming growth factor beta 1 (TGFß1). PB treatment in vivo or in vitro elevated the production and release of tumor necrosis factor alpha from MC, which was identified as mainly responsible for the inhibition of apoptosis in HC. In conclusion, our findings reveal profound proinflammatory effects of PB on hepatic mesenchyme and mesenchymal-epithelial interactions. The resulting release of cytokines acts antiapoptotic in HC, an effect crucial for tumor promotion and carcinogenesis by NGC.
Carbon Centered Trigonal Prismatic Tungsten Clusters [W6CCl18]n– (n = 1, 2) containing Copper(I) and Copper(II)
2015-09-16

Abstract The solid state reaction of WCl 6 with copper powder and a reactive source of carbon leads to a new trigonal prismatic carbon‐centered tungsten cluster containing copper ions. Cu[W 6 CCl 18 ] dissolves in organic solvents (dimethylsulfoxide, acetone), resulting in two air stable products Cu(C 2 H 6 OS) 6 [W 6 CCl 18 ] and Cu(C 2 H 6 OS) 4 [W 6 CCl 18 ] 2 . Both of them contain carbon‐centered trigonal prismatic tungsten clusters [W 6 CCl 18 ] n – ( n = 1, 2) and Jahn‐Teller distorted octahedral copper(II) ions. Crystal structures of all compounds were investigated by single‐crystal X‐ray diffraction. The presence of carbon as an interstitial atom in the cluster is confirmed by nuclear magnetic resonance spectroscopy.
Recessive mutations inSLC13A5result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia
2015-09-17

The epileptic encephalopathies are a clinically and aetiologically heterogeneous subgroup of epilepsy syndromes. Most epileptic encephalopathies have a genetic cause and patients are often found to carry a heterozygous de novo mutation in one of the genes associated with the disease entity. Occasionally recessive mutations are identified: a recent publication described a distinct neonatal epileptic encephalopathy (MIM 615905) caused by autosomal recessive mutations in the SLC13A5 gene. Here, we report eight additional patients belonging to four different families with autosomal recessive mutations in SLC13A5. SLC13A5 encodes a high affinity sodium-dependent citrate transporter, which is expressed in the brain. Neurons are considered incapable of de novo synthesis of tricarboxylic acid cycle intermediates; therefore they rely on the uptake of intermediates, such as citrate, to maintain their energy status and neurotransmitter production. The effect of all seven identified mutations (two premature stops and five amino acid substitutions) was studied in vitro, using immunocytochemistry, selective western blot and mass spectrometry. We hereby demonstrate that cells expressing mutant sodium-dependent citrate transporter have a complete loss of citrate uptake due to various cellular loss-of-function mechanisms. In addition, we provide independent proof of the involvement of autosomal recessive SLC13A5 mutations in the development of neonatal epileptic encephalopathies, and highlight teeth hypoplasia as a possible indicator for SLC13A5 screening. All three patients who tried the ketogenic diet responded well to this treatment, and future studies will allow us to ascertain whether this is a recurrent feature in this severe disorder.
Molecular epidemiology and surveillance of circulating rotavirus and adenovirus in Congolese children with gastroenteritis
2015-09-17

Infectious Diarrhea caused by rotavirus and adenovirus, is a leading cause of death in children in sub‐Sahara Africa but there is limited published data on the diverse rotavirus genotypes and adenovirus serotypes circulating in the Republic of Congo. In this study, we investigated the prevalence of severe diarrhea caused by rotavirus A (RVA) and Adenovirus serotype 40 and 41 in Congolese children hospitalized with severe gastroenteritis. Stool samples were collected from 655 Congolese children less than 60 months of age hospitalized with acute gastroenteritis between June 2012 and June 2013. Rotavirus and adenovirus antigens were tested using commercially available ELISA kits and the RVA G‐ and P‐ genotypes were identified by seminested multiplex RT‐PCR. Three hundred and four (46.4%) children were tested positive for RVA. Adenovirus infection was found in 5.5% of the 564 tested children. Rotavirus infection was frequently observed in children between 6–12 months (55.9%). The dry season months recorded increased RVA infection while no seasonality of adenovirus infection was demonstrated. The most common RVA genotypes were G1 (57.5%), G2 (6.4%), G1G2 mixture (15.5%), P[8] (58%), P[6] (13.2%), and P[8]P[6] mixture (26%). Additionally, the genotype G12P[6] was significantly associated with increased vomiting. This first study on Congolese children demonstrates a high prevalence and clinical significance of existing rotavirus genotypes. Adenovirus prevalence is similar to that of other Central African countries. This baseline epidemiology and molecular characterization study will contribute significantly to the RVA surveillance after vaccine implementation in the country. J. Med. Virol. 88:596–605, 2016 . © 2015 Wiley Periodicals, Inc.
Experimental and Theoretical Evaluation of the Ethynyl Moiety as a Halogen Bioisostere
2015-09-17

Bioisosteric replacements are widely used in medicinal chemistry to improve physicochemical and ADME properties of molecules while retaining or improving affinity. Here, using the p53 cancer mutant Y220C as a test case, we investigate both computationally and experimentally whether an ethynyl moiety is a suitable bioisostere to replace iodine in ligands that form halogen bonds with the protein backbone. This bioisosteric transformation is synthetically feasible via Sonogashira cross-coupling. In our test case of a particularly strong halogen bond, replacement of the iodine with an ethynyl group resulted in a 13-fold affinity loss. High-resolution crystal structures of the two analogues in complex with the p53-Y220C mutant enabled us to correlate the different affinities with particular features of the binding site and subtle changes in ligand binding mode. In addition, using QM calculations and analyzing the PDB, we provide general guidelines for identifying cases where such a transformation is likely to improve ligand recognition.
B7-H1 Selectively Controls TH17 Differentiation and Central Nervous System Autoimmunity via a Novel Non–PD-1–Mediated Pathway
2015-09-17

Abstract It is currently acknowledged that TH17 cells are critically involved in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). In this article, we demonstrate that signals delivered by the coinhibitory molecule B7-homologue 1 (B7-H1) via a B7-homologue 1 mouse-IgG2aFc (B7-H1-Ig) fusion protein nearly abolish TH17, but not TH1 and TH2, differentiation via direct interaction with the T cell. These effects were equally pronounced in the absence of programmed death-1 or B7.1 and B7.2 on the T cell side, thus providing clear evidence that B7-H1 modulates T cell differentiation via a novel receptor. Mechanistically, B7-H1 interfered with early TCR-mediated signaling and cytokine-mediated induction of the TH17-determining transcription factors retinoic acid-related orphan receptor γ t and IFN regulator factor-4 in a programmed death-1 and B7-independent fashion. In an animal model of MS, active myelin oligodendrocyte glycoprotein–induced experimental autoimmune encephalomyelitis, B7-H1-Ig exhibited a significant and long-lasting effect on disease severity upon administration during the first 5 d of the priming phase, which was accompanied by reduced TH17 responses in the periphery and within the CNS. Importantly, B7-H1-Ig was even capable of interfering with T cell encephalitogenicity when interaction with the T cells occurred after priming using an adoptive transfer experimental autoimmune encephalomyelitis model. In line with this, both naive human CD4+ T cells and differentiated TH17 effector cells from MS patients were highly sensitive toward B7-H1-Ig–mediated TH17 suppression. Together, we propose the existence of a novel B7-H1–mediated immune-regulatory pathway in T cells, which selectively limits murine and human TH17 cell responses and might be therapeutically exploited to control TH17-mediated autoimmunity.
Using elliptical best fits to characterize dental shapes
2015-09-18

ABSTRACT A variety of geometric morphometric methods have recently been used to describe dental shape variation in human evolutionary studies. However, the applicability of these methods is limited when teeth are worn or are difficult to orient accurately. Here we show that elliptical best fits on outlines of dental tissues below the crown provide basic size‐ and orientation‐free shape descriptors. Using the dm 2 and M 3 as examples, we demonstrate that these descriptors can be used for taxonomic purposes, such as distinguishing between Neanderthal and recent modern human teeth. We propose that this approach can be a useful alternative to existing methodology. Am J Phys Anthropol 159:342–347, 2016. © 2015 Wiley Periodicals, Inc.
Hydrodynamic resonance in optical traps & friction of molecular machines
2015-09-18

Optical tweezers are high-resolution position and force transducers widely used in physics, material science and biology. Often dielectric particles of mesoscopic size are used as sensitive probes and handles for experiments. We designed and fabricated high-refractive index, anti-reflection coated titania microspheres (Fig. 1, [1]) and demonstrated nanonewton optical forces [2]. Using the coated microspheres, novel experiments are feasible. The high trap stiffness enabled us to directly measure the colored nature of noise that drives Brownian motion and how it depends on the distance to a nearby surface in quantitative agreement with theoretical predictions [3]. This hydrodynamic resonance can be increased by using larger particles and/or lower viscosity fluids. I will show our efforts in increasing the amplitude of this resonance peak.
Predictors of preoperative and early postoperative seizures in patients with intra‐axial primary and metastatic brain tumors: A retrospective observational single center study
2015-09-19

Objective Antiepileptic treatment of brain tumor patients mainly depends on the individual physician's choice rather than on well‐defined predictive factors. We investigated the predictive value of defined clinical parameters to formulate a model of risk estimations for subpopulations of brain tumor patients. Methods We enclosed 650 patients &gt; 18 years of age who underwent brain tumor surgery and included a number of clinical data. Logistic regressions were performed to determine the effect sizes of seizure‐related risk factors and to develop prognostic scores for the occurrence of preoperative and early postoperative seizures. Results A total of 492 patients (334 gliomas) were eligible for logistic regression for preoperative seizures, and 338 patients for early postoperative seizures. Age ≤ 60 years (odds ratio [OR] = 1.66, p = 0.020), grades I and II glioma (OR = 4.00, p = 0.0002), total tumor/edema volume ≤ 64cm 3 (OR = 2.18, p = 0.0003), and frontal location (OR = 2.28, p = 0.034) demonstrated an increased risk for preoperative seizures. Isocitrate–dehydrogenase mutations (OR = 2.52, p = 0.026) were an independent risk factor in the glioma subgroup. Age ≥ 60 years (OR = 3.32, p = 0.041), total tumor/edema volume ≤ 64cm 3 (OR = 3.17, p = 0.034), complete resection (OR = 15.50, p = 0.0009), diencephalic location (OR = 12.2, p = 0.013), and high‐grade tumors (OR = 5.67, p = 0.013) were significant risk factors for surgery‐related seizures. Antiepileptics (OR = 1.20, p = 0.60) did not affect seizure occurrence. For seizure occurrence, patients could be stratified into 3 prognostic preoperative and into 2 prognostic early postoperative groups. Interpretation Based on the developed prognostic scores, seizure prophylaxis should be considered in high‐risk patients and patient stratification for prospective studies may be feasible in the future. Ann Neurol 2015;78:917–928