julilili42/papers huggingface dataset:
Dissociation of GLP-1 and insulin association with food processing in the brain: GLP-1 sensitivity despite insulin resistance in obese humans
2015-10-02

The postprandial release of GLP-1 might alter reward processes in the orbitofrontal cortex and might thereby support the termination of food intake and reduce hunger. While obese persons showed brain insulin resistance, no GLP-1 resistance was observed. Our study provides novel insight into the central regulation of food intake by the incretin hormone GLP-1.
Identification and activation of novel biosynthetic gene clusters by genome mining in the kirromycin producer Streptomyces collinus Tü 365
2015-10-03

Abstract Streptomycetes are prolific sources of novel biologically active secondary metabolites with pharmaceutical potential. S. collinus Tü 365 is a Streptomyces strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of the antibiotic kirromycin, an inhibitor of the protein biosynthesis interacting with elongation factor EF-Tu. Genome Mining revealed 32 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of Streptomyces collinus Tü 365, indicating an enormous biosynthetic potential of this strain. The structural diversity of secondary metabolisms predicted for S. collinus Tü 365 includes PKS, NRPS, PKS-NRPS hybrids, a lanthipeptide, terpenes and siderophores. While some of these gene clusters were found to contain genes related to known secondary metabolites, which also could be detected in HPLC–MS analyses, most of the uncharacterized gene clusters are not expressed under standard laboratory conditions. With this study we aimed to characterize the genome information of S. collinus Tü 365 to make use of gene clusters, which previously have not been described for this strain. We were able to connect the gene clusters of a lanthipeptide, a carotenoid, five terpenoid compounds, an ectoine, a siderophore and a spore pigment-associated gene cluster to their respective biosynthesis products.
Enzyme-Powered Hollow Mesoporous Janus Nanomotors
2015-10-05

The development of synthetic nanomotors for technological applications in particular for life science and nanomedicine is a key focus of current basic research. However, it has been challenging to make active nanosystems based on biocompatible materials consuming nontoxic fuels for providing self-propulsion. Here, we fabricate self-propelled Janus nanomotors based on hollow mesoporous silica nanoparticles (HMSNPs), which are powered by biocatalytic reactions of three different enzymes: catalase, urease, and glucose oxidase (GOx). The active motion is characterized by a mean-square displacement (MSD) analysis of optical video recordings and confirmed by dynamic light scattering (DLS) measurements. We found that the apparent diffusion coefficient was enhanced by up to 83%. In addition, using optical tweezers, we directly measured a holding force of 64 ± 16 fN, which was necessary to counteract the effective self-propulsion force generated by a single nanomotor. The successful demonstration of biocompatible enzyme-powered active nanomotors using biologically benign fuels has a great potential for future biomedical applications.
Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide
2015-10-05

Significance Fungi increasingly cause serious medical problems in immunocompromised populations. Antimicrobial peptides are primary effector molecules of innate immune systems. Antimicrobial peptides successfully protect healthy humans from bacterial infections. However, it is largely unknown how and why human body surfaces resist fungal infections. We identified the common epithelial protein, psoriasin (S100A7), in its disulphide-reduced form (redS100A7) as the principal antifungal factor of human body surfaces. redS100A7 kills several pathogenic fungi using a mechanism that differs from conventional antifungal agents. Thus, this study might contribute to a better understanding of human defense systems against fungal infection and the development of urgently needed novel antifungal therapeutics.
pROC-Chemotype Plots Enhance the Interpretability of Benchmarking Results in Structure-Based Virtual Screening
2015-10-05

Recently, we have reported a systematic comparison of molecular preparation protocols (using MOE or Maestro) in combination with two docking tools (GOLD or Glide), employing our DEKOIS 2.0 benchmark sets. Herein, we demonstrate how comparable settings of data preparation protocols can affect the profile and AUC of pROC curves based on variations in chemotype enrichment. We show how the recognition of different classes of chemotypes can affect the docking performance, particularly in the early enrichment, and monitor changes in this recognition behavior based on score normalization and rescoring strategies. For this, we have developed "pROC-Chemotype", which is an automated protocol that matches and visualizes ligand chemotype information together with potency classes in the pROC profiles obtained by docking. This tool enhances the understanding of the influence of chemotype recognition in early enrichment, but also reveals trends of impaired recognition of chemotype classes at the end of the score-ordered rank. Identifying such issues helps to devise score-normalization strategies to overcome this potential bias in an intuitive manner. Furthermore, strong perturbations in chemotype ranking between different methods can help to identify the underlying reasons (e.g., changes in the protonation/tautomerization state). It also assists in the selection of appropriate scoring functions that are capable to retrieve more potent and diverse hits. In summary, we demonstrate how this new tool can be utilized to identify and highlight chemotype-specific behavior, e.g., in dataset preparation. This can help to overcome some chemistry-related bias in virtual screening campaigns. pROC-Chemotype is made freely available at www.dekois.com.
The International Criminal Court in Ongoing Intrastate Conflicts
2015-10-05

In recent decades, international courts have increasingly started investigating armed conflicts. However, the impact of this remains under-researched. Patrick S. Wegner closes this gap via a comprehensive analysis of the impact of the International Criminal Court in the Darfur and Lord&amp;apos;s Resistance Army conflicts. He offers a fresh approach to peace and conflict studies, while avoiding the current quantitative focus of the literature and polarisation between critics and supporters of applying justice in conflicts. This is the first time that the impact of an international criminal court has been analysed in all its facets in two conflicts. The consequences of these investigations are much more complex and difficult to predict than most of the existing literature suggests. Recurrent claims, such as the deterrent effect of trials and the danger of blocking negotiations by the issuing of arrest warrants, are put to the test here with some surprising results.
Influence of the Retinal Blood Vessel Topography on the Variability of the Retinal Nerve Fiber Bundle Trajectories in the Human Retina
2015-10-05

The retinal blood vessel topography explains a significant part of the RNFB trajectory variability but only if (1) the vessel topography is assessed at an appropriate distance from the ONH and (2) the superior and inferior hemifield are addressed independently.
Synthesis of Inert Homo- and Heterodinuclear Rare-Earth Cryptates
2015-10-05

A new ditopic cryptand based on two tris(biaryl)-based binding pockets bridged by a 2,2'-bipyrimidine unit enables the selective synthesis of homo- and heterodinuclear rare-earth cryptates, which are kinetically inert under challenging conditions and can even be purified by preparative high-performance liquid chromatography.
Refined Method for Droplet Microfluidics-Enabled Detection of Plasmodium falciparum Encoded Topoisomerase I in Blood from Malaria Patients
2015-10-05

Rapid and reliable diagnosis is essential in the fight against malaria, which remains one of the most deadly infectious diseases in the world. In the present study we take advantage of a droplet microfluidics platform combined with a novel and user-friendly biosensor for revealing the main malaria-causing agent, the Plasmodium falciparum (P. falciparum) parasite. Detection of the parasite is achieved through detection of the activity of a parasite-produced DNA-modifying enzyme, topoisomerase I (pfTopoI), in the blood from malaria patients. The assay presented has three steps: (1) droplet microfluidics-enabled extraction of active pfTopoI from a patient blood sample; (2) pfTopoI-mediated modification of a specialized DNA biosensor; (3) readout. The setup is quantitative and specific for the detection of Plasmodium topoisomerase I. The procedure is a considerable improvement of the previously published Rolling Circle Enhanced Enzyme Activity Detection (REEAD) due to the advantages of involving no signal amplification steps combined with a user-friendly readout. In combination these alterations represent an important step towards exploiting enzyme activity detection in point-of-care diagnostics of malaria.
3D hydrodynamic simulations of the Galactic supernova remnant CTB 109
2015-10-05

\\n Context. Using detailed 3D hydrodynamic simulations we study the nature of the Galactic supernova remnant (SNR) <ext-link ext-link-type="aoi">CTB 109</ext-link> (G109.1-1.0), which is well known for its semicircular shape and a bright diffuse X-ray emission feature inside the SNR. \\n Aims. Our model has been designed to explain the observed morphology, with a special emphasis on the bright emission feature inside the SNR. Moreover, we determine the age of the remnant and compare our findings with X-ray observations. With CTB 109 we test a new method of detailed numerical simulations of diffuse young objects, using realistic initial conditions derived directly from observations. \\n Methods. We performed numerical 3D simulations with the RAMSES code. The initial density structure has been directly taken from 12CO emission data, adding an additional dense cloud, which, when it is shocked, causes the bright emission feature. \\n Results. From parameter studies we obtained the position (l,b) = (109.1545°,−1.0078°) for an elliptical cloud with ncloud = 25 cm-3 based on the preshock density from Chandra data and a maximum diameter of 4.54 pc, whose encounter with the supernova (SN) shock wave generates the bright X-ray emission inside the SNR. The calculated age of the remnant is about 11 000 yr according to our simulations. In addition, we can also determine the most probable site of the SN explosion. \\n Conclusions. Hydrodynamic simulations can reproduce the morphology and the observed size of the SNR CTB 109 remarkably well. Moreover, the simulations show that it is very plausible that the bright X-ray emission inside the SNR is the result of an elliptical dense cloud shocked by the SN explosion wave. We show that numerical simulations using observational data for an initial model can produce meaningful results. \\n
Liver fluke‐infested graft used for living‐donor liver transplantation: case report and review of the literature
2015-10-05

Abstract Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also known as liver flukes. Clonorchiasis is endemic in a wide geographical area extending from Eastern Europe to Southeast Asia. Infested hosts may remain asymptomatic for decades and consequently their liver can become available as a graft. To date, 20 liver transplantations with liver fluke‐infested grafts have been reported in the literature. All of them occurred in Asian countries. We, here, report the first case to our knowledge in the Western world of living‐donor liver transplantation ( LDLT ) with an O pisthorchis felineus ‐infested graft, and present a review of the literature. A 6‐month‐old girl with decompensated secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested with O . felineus . After prompt diagnosis and adequate therapy, both donor and recipient had an uneventful postoperative course and long‐term follow‐up. Liver grafts infested with liver flukes do not pose a contraindication to liver donation from deceased or living donors, provided that a correct diagnosis and treatment are performed in a timely fashion.
Global Perspectives on Economics and Biology
2015-10-05

Abstract This chapter traces global trends in physical stature from the Neolithic Agricultural Revolution to modern times. Major cycles in nutritional status and the biological standard of living can be documented across the course of human history as the amount and quality of nutrition changed. In addition, inequality of living standards increased in the more stratified societies that came into being after the Agricultural Revolution. A second major transformation of living standards began with the Industrial Revolution, putting strain on the biological living standards of many populations, especially when accompanied by population growth, market integration, and rising inequality. A rapid increase in physical stature began in Europe only after the 1870s, about a century after the beginning of modern economic growth. Global studies on height inequality indicate a long-run decline of inequality during the late 19th and early 20th century in Europe. Inequality trends are related to important societal-level outcomes.
On Reducing the Phong Shading Method
2015-10-05

Today, the shading method of Phong plays an important role in the design of realtime image generation systems. Often, the model has been used in combination with a color interpolation, suppressing a main property of this model, namely the visually acceptable rendering of highlights. Unfortunately, Phong’s algorithm demands a normalization, which is expensive to implement in hardware. We will present several shading methods which are reductions of the Phong algorithm. They will be compared both visually and theoretically. The alternatives are judged concerning their costs for a hardware implementation. The result is a hierarchy of shading methods that can be used to select the required cost-performance ratio for a given visualization task.
TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst
2015-10-06

Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second major histocompatibility complex (MHC) class I-specific chaperone. We sought to determine whether, like tapasin, TAPBPR can also influence MHC class I peptide selection by functioning as a peptide exchange catalyst. We show that TAPBPR can catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the loading of peptide-receptive MHC I molecules, and discriminate between peptides based on affinity in vitro. In cells, the depletion of TAPBPR increased the diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is involved in restricting peptide presentation. Our results suggest TAPBPR binds to MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide optimisation. It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system.
The Genetic Variant I148M inPNPLA3Is Associated With Increased Hepatic Retinyl-Palmitate Storage in Humans
2015-10-06

The increased content of hepatic retinyl-palmitate and the reduced ratio of retinol/retinyl-palmitate in PNPLA3 I148M minor allele carriers support in vitro findings of an altered retinyl-palmitate lipase activity. Our results indicate that the PNPLA3 I148M variant is relevant for the retinyl-palmitate content in human liver, providing a possible link to chronic liver disease.
Streptocollin, a Type IV Lanthipeptide Produced by Streptomyces collinus Tü 365
2015-10-06

Abstract Lanthipeptides are ribosomally synthesized and post‐translationally modified microbial secondary metabolites. Here, we report the identification and isolation of streptocollin from Streptomyces collinus Tü 365, a new member of class IV lanthipeptides. Insertion of the constitutive ermE * promoter upstream of the lanthipeptide synthetase gene stcL resulted in peptide production. The streptocollin gene cluster was heterologously expressed in S. coelicolor M1146 and M1152 with 3.5‐ and 5.5‐fold increased yields, respectively. The structure and ring topology of streptocollin were determined by high resolution MS/MS analysis. Streptocollin contains four macrocyclic rings, with one lanthionine and three methyllanthionine residues. To the best of our knowledge, this is the first report on the isolation of a class IV lanthipeptide in preparative amounts, and on the successful heterologous expression of a class IV lanthipeptide gene cluster.
Combining 3D Hydraulic Tomography with Tracer Tests for Improved Transport Characterization
2015-10-06

Abstract Hydraulic tomography ( HT ) is a method for resolving the spatial distribution of hydraulic parameters to some extent, but many details important for solute transport usually remain unresolved. We present a methodology to improve solute transport predictions by combining data from HT with the breakthrough curve ( BTC ) of a single forced‐gradient tracer test. We estimated the three dimensional ( 3D ) hydraulic‐conductivity field in an alluvial aquifer by inverting tomographic pumping tests performed at the Hydrogeological Research Site Lauswiesen close to Tübingen, Germany, using a regularized pilot‐point method. We compared the estimated parameter field to available profiles of hydraulic‐conductivity variations from direct‐push injection logging ( DPIL ), and validated the hydraulic‐conductivity field with hydraulic‐head measurements of tests not used in the inversion. After validation, spatially uniform parameters for dual‐domain transport were estimated by fitting tracer data collected during a forced‐gradient tracer test. The dual‐domain assumption was used to parameterize effects of the unresolved heterogeneity of the aquifer and deemed necessary to fit the shape of the BTC using reasonable parameter values. The estimated hydraulic‐conductivity field and transport parameters were subsequently used to successfully predict a second independent tracer test. Our work provides an efficient and practical approach to predict solute transport in heterogeneous aquifers without performing elaborate field tracer tests with a tomographic layout.
p21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase
2015-10-06

Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 2 (PREX2) is a guanine nucleotide exchange factor (GEF) for the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase, facilitating the exchange of GDP for GTP on Rac1. GTP-bound Rac1 then activates its downstream effectors, including p21-activated kinases (PAKs). PREX2 and Rac1 are frequently mutated in cancer and have key roles within the insulin-signaling pathway. Rac1 can be inactivated by multiple mechanisms; however, negative regulation by insulin is not well understood. Here, we show that in response to being activated after insulin stimulation, Rac1 initiates its own inactivation by decreasing PREX2 GEF activity. Following PREX2-mediated activation of Rac1 by the second messengers PIP3 or Gβγ, we found that PREX2 was phosphorylated through a PAK-dependent mechanism. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. Cell fractionation experiments also revealed that phosphorylation prevented PREX2 from localizing to the cellular membrane. Furthermore, the onset of insulin-induced phosphorylation of PREX2 was delayed compared with AKT. Altogether, we propose that second messengers activate the Rac1 signal, which sets in motion a cascade whereby PAKs phosphorylate and negatively regulate PREX2 to decrease Rac1 activation. This type of regulation would allow for transient activation of the PREX2-Rac1 signal and may be relevant in multiple physiological processes, including diseases such as diabetes and cancer when insulin signaling is chronically activated.
NDRG2 phosphorylation provides negative feedback for SGK1-dependent regulation of a kainate receptor in astrocytes
2015-10-06

Glutamate receptors play an important role in the function of astrocytes. Among their tasks is the regulation of gliotransmission, gene expression and exocytosis of the tissue-type plasminogen activator (tPA), which has an enhancing effect on N-methyl-D-aspartate (NMDA) receptors and thus prevent over-excitation of neighboring neurons. The kainate receptor GluK2, which is expressed in neurons and astrocytes, is under tight regulation of the PI3-kinase SGK pathway as shown in neurons. SGK1 targets include N-myc downstream-regulated genes (NDRGs) 1 and 2 (NDRG1, NDRG2), proteins with elusive function. In the present study, we analyzed the effects of SGK1, NDRG1, and NDRG2 on GluK2 current amplitude and plasma membrane localization in astrocytes and heterologous expression. We demonstrate that NDRG1 and NDRG2 themselves have no effect on GluK2 current amplitudes in heterologous expressed ion channels. However, when NDRG2 is coexpressed with GluK2 and SGK1, the stimulating effect of SGK1 on GluK2 is suppressed both in heterologous expression and in astrocytes. Here, we reveal a new negative feedback mechanism, whereby GluK2 stimulation by SGK1 is regulated by parallel phosphorylation of NDRG2. This regulation of GluK2 by SGK1 and NDRG2 in astrocytes may play an important role in gliotransmission, modulation of gene expression and regulation of exocytosis of tPA.