julilili42/papers huggingface dataset:
Effect of X-ray irradiation on ancient DNA in sub-fossil bones – Guidelines for safe X-ray imaging
2016-06-08

Abstract Sub-fossilised remains may still contain highly degraded ancient DNA (aDNA) useful for palaeogenetic investigations. Whether X-ray computed [micro-] tomography ([μ]CT) imaging of these fossils may further damage aDNA remains debated. Although the effect of X-ray on DNA in living organisms is well documented, its impact on aDNA molecules is unexplored. Here we investigate the effects of synchrotron X-ray irradiation on aDNA from Pleistocene bones. A clear correlation appears between decreasing aDNA quantities and accumulating X-ray dose-levels above 2000 Gray (Gy). We further find that strong X-ray irradiation reduces the amount of nucleotide misincorporations at the aDNA molecule ends. No representative effect can be detected for doses below 200 Gy. Dosimetry shows that conventional μCT usually does not reach the risky dose level, while classical synchrotron imaging can degrade aDNA significantly. Optimised synchrotron protocols and simple rules introduced here are sufficient to ensure that fossils can be scanned without impairing future aDNA studies.
Systemic therapy in metastatic renal cell carcinoma
2016-06-09

Despite the high level of evidence for first and second-line treatment in mRCC, data for third-line therapy are limited. Possible sequences include TKI-mTOR-TKI or TKI-TKI-mTOR with the upcoming checkpoint inhibitors in perspective, which might settle a new standard of care after previous TKI therapy.
MicroRNAs regulate T‐cell production of interleukin‐9 and identify hypoxia‐inducible factor‐2α as an important regulator of T helper 9 and regulatory T‐cell differentiation
2016-06-09

Summary Micro RNA s (miRNAs) regulate many aspects of helper T cell (Th) development and function. Here we found that they are required for the suppression of interleukin‐9 ( IL ‐9) expression in Th9 cells and other Th subsets. Two highly related mi RNA s (miR‐15b and miR‐16) that we previously found to play an important role in regulatory T (Treg) cell differentiation were capable of suppressing IL ‐9 expression when they were over‐expressed in Th9 cells. We used these mi RNA s as tools to identify novel regulators of IL ‐9 expression and found that they could regulate the expression of Epas1 , which encodes hypoxia‐inducible factor ( HIF )‐2 α . HIF proteins regulate metabolic pathway usage that is important in determining appropriate Th differentiation. The related protein, HIF ‐1 α enhances Th17 differentiation and inhibits Treg cell differentiation. Here we found that HIF ‐2 α was required for IL ‐9 expression in Th9 cells, but its expression was not sufficient in other Th subsets. Furthermore, HIF ‐2 α suppressed Treg cell differentiation like HIF ‐1 α , demonstrating both similar and distinct roles of the HIF proteins in Th differentiation and adding a further dimension to their function. Ironically, even though miR‐15b and miR‐16 suppressed HIF ‐2 α expression in Treg cells, inhibiting their function in Treg cells did not lead to an increase in IL ‐9 expression. Therefore, the physiologically relevant mi RNA s that regulate IL ‐9 expression in Treg cells and other subsets remain unknown. Nevertheless, the analysis of miR‐15b and miR‐16 function led to the discovery of the importance of HIF ‐2 α so this work demonstrated the utility of studying mi RNA function to identify novel regulatory pathways in helper T‐cell development.
Bezafibrate Improves Insulin Sensitivity and Metabolic Flexibility in STZ-Induced Diabetic Mice
2016-06-09

Bezafibrate (BEZ), a pan activator of peroxisome proliferator–activated receptors (PPARs), has been generally used to treat hyperlipidemia for decades. Clinical trials with type 2 diabetes patients indicated that BEZ also has beneficial effects on glucose metabolism, although the underlying mechanisms of these effects remain elusive. Even less is known about a potential role for BEZ in treating type 1 diabetes. Here we show that BEZ markedly improves hyperglycemia and glucose and insulin tolerance in mice with streptozotocin (STZ)-induced diabetes, an insulin-deficient mouse model of type 1 diabetes. BEZ treatment of STZ mice significantly suppressed the hepatic expression of genes that are annotated in inflammatory processes, whereas the expression of PPAR and insulin target gene transcripts was increased. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Finally, we show that the number of pancreatic islets and the area of insulin-positive cells tended to be higher in BEZ-treated mice. Our data suggest that BEZ may improve impaired glucose metabolism by augmenting hepatic mitochondrial performance, suppressing hepatic inflammatory pathways, and improving insulin sensitivity and metabolic flexibility. Thus, BEZ treatment might also be useful for patients with impaired glucose tolerance or diabetes.
Toward Leiodermatolide: Synthesis of the Core Structure
2016-06-09

The macrocyclic core (35) of the marine natural product leiodermatolide (1) was synthesized from two key fragments, vinyl iodide 23 (C1-C11 part) and vinyl stannane 31 (C12-C18 part). A Stille coupling led to conjugated Z,Z-diene 32. The derived seco acid 34 was cyclized using a Yamaguchi macrolactonization. Key steps in the assembly of vinyl iodide 23 were a Paterson aldol reaction, and a Kumada coupling on a triflate derivative to create the C4-C5 trisubstituted double bond. The two stereocenters in fragment 31 were established by a Marshall-Tamaru reaction. The longest linear sequence comprises 20 steps.
Structure of the host-recognition device of Staphylococcus aureus phage ϕ11
2016-06-10

Abstract Phages play key roles in the pathogenicity and adaptation of the human pathogen Staphylococcus aureus . However, little is known about the molecular recognition events that mediate phage adsorption to the surface of S. aureus . The lysogenic siphophage φ11 infects S. aureus SA113. It was shown previously that φ11 requires α- or β-N-acetylglucosamine (GlcNAc) moieties on cell wall teichoic acid (WTA) for adsorption. Gp45 was identified as the receptor binding protein (RBP) involved in this process and GlcNAc residues on WTA were found to be the key component of the φ11 receptor. Here we report the crystal structure of the RBP of φ11, which assembles into a large, multidomain homotrimer. Each monomer contains a five-bladed propeller domain with a cavity that could accommodate a GlcNAc moiety. An electron microscopy reconstruction of the φ11 host adhesion component, the baseplate, reveals that six RBP trimers are assembled around the baseplate core. The Gp45 and baseplate structures provide insights into the overall organization and molecular recognition process of the phage φ11 tail. This assembly is conserved among most glycan-recognizing Siphoviridae , and the RBP orientation would allow host adhesion and infection without an activation step.
EEG Responses to Auditory Stimuli for Automatic Affect Recognition
2016-06-10

Brain state classification for communication and control has been well established in the area of brain-computer interfaces over the last decades. Recently, the passive and automatic extraction of additional information regarding the psychological state of users from neurophysiological signals has gained increased attention in the interdisciplinary field of affective computing. We investigated how well specific emotional reactions, induced by auditory stimuli, can be detected in EEG recordings. We introduce an auditory emotion induction paradigm based on the International Affective Digitized Sounds 2nd Edition (IADS-2) database also suitable for disabled individuals. Stimuli are grouped in three valence categories: unpleasant, neutral, and pleasant. Significant differences in time domain domain event-related potentials are found in the electroencephalogram (EEG) between unpleasant and neutral, as well as pleasant and neutral conditions over midline electrodes. Time domain data were classified in three binary classification problems using a linear support vector machine (SVM) classifier. We discuss three classification performance measures in the context of affective computing and outline some strategies for conducting and reporting affect classification studies.
Structural Evolution of Metastable Protein Aggregates in the Presence of Trivalent Salt Studied by (V)SANS and SAXS
2016-06-10

We present a study of the structural evolution of protein aggregates formed in solutions of a globular protein, β-lactoglobulin (BLG), in the presence of YCl3. These aggregates are often observed before crystallization starts and they are metastable with respect to the crystalline phase. Here we focus on the characterization of the hierarchical structure of this intermediate phase and its temperature dependent structure evolution using a combination of (very) small angle neutron and X-ray scattering (VSANS, SANS, and SAXS). Results show that the hierarchical structure ranges from nanometer scale protein monomer, dimer and compact protein clusters to micrometer scale fractal protein aggregates. Upon cooling, the overall hierarchical structure is preserved, but the evolution of the internal structure within the aggregates is clearly visible: the monomer–monomer correlation peak reduces its intensity and disappears completely at lower temperatures, whereas the cluster–cluster correlation is enhanced. At a larger length scale, the fractal dimension of protein aggregates increases. The kinetics of the structure change during a temperature ramp was further investigated using time-resolved SAXS. The time dependent SAXS profiles show clear isosbestic points and the kinetics of the structural evolution can be well described using a two-state model. These dynamic properties of protein aggregates on a broad length scale may be essential for being the precursors of nucleation.
Validity of longitudinal sections for determining the apical constriction
2016-06-10

Abstract Aim To validate the use of longitudinal sections against cross sections using micro‐ CT for disclosing the topography and location of the apical constriction. Methodology Seventy extracted human teeth with 117 completely developed roots were micro‐ CT scanned and reconstructed at a voxel size of 27 μm. The 3 DS licer program was used to navigate the longitudinal sections parallel to the long axis of the canal and also to rotate and tilt the views. Each root canal was evaluated in both mesio‐distal and bucco‐lingual planes. Constriction topographies were identified as described in the literature. In each canal, the number of different topographies detected was recorded. Further, serial cross‐sectional analysis of the apical portion of the canal was performed. Reconstructed plots of canal areas were assessed to locate the constriction and determine its form. A descriptive analysis of both longitudinal and cross section methods was conducted. In each canal, the frequency of constriction forms was calculated in the mesio‐distal or bucco‐lingual aspects and the 99% confidence interval was computed. Results When both aspects of the longitudinal sections were pooled, all root canals had two or more topographies and consequently different locations of the apical constriction. In contrast, cross‐sectional analysis constantly yielded one constriction form per canal. Conclusion Compared to cross‐sectional analysis, longitudinal sections of the root canal conveyed inconsistent results regarding the topography and the location of the apical constriction.
Hypothyroidism during second-line treatment of multidrug-resistant tuberculosis: a prospective study
2016-06-10

TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.
Mixed parity pairing in a dipolar gas
2016-06-10

We show that fermionic dipoles in a two-layer geometry form Cooper pairs with both singlet and triplet components, when they are tilted with respect to the normal of the planes. The mixed parity pairing arises because the interaction between dipoles in the two different layers is not inversion symmetric. We use an efficient eigenvalue approach to calculate the zero temperature phase diagram of the system as a function of the dipole orientation and the layer distance. The phase diagram contains purely triplet as well as mixed singlet and triplet superfluid phases. We show in detail how the pair wave function for dipoles residing in different layers smoothly changes from singlet to triplet symmetry as the orientation of the dipoles is changed. Our results indicate that dipolar quantum gases can be used to unambiguously observe mixed parity pairing.
The Planar Tree Packing Theorem
2016-06-10

Packing graphs is a combinatorial problem where several given graphs are being mapped into a common host graph such that every edge is used at most once. In the planar tree packing problem we are given two trees T1 and T2 on n vertices and have to find a planar graph on n vertices that is the edge-disjoint union of T1 and T2. A clear exception that must be made is the star which cannot be packed together with any other tree. But according to a conjecture of Garcia et al. from 1997 this is the only exception, and all other pairs of trees admit a planar packing. Previous results addressed various special cases, such as a tree and a spider tree, a tree and a caterpillar, two trees of diameter four, two isomorphic trees, and trees of maximum degree three. Here we settle the conjecture in the affirmative and prove its general form, thus making it the planar tree packing theorem. The proof is constructive and provides a polynomial time algorithm to obtain a packing for two given nonstar trees.
Combined hybridization capture and shotgun sequencing for ancient DNA analysis of extinct wild and domestic dromedary camel
2016-06-11

Abstract The performance of hybridization capture combined with next‐generation sequencing ( NGS ) has seen limited investigation with samples from hot and arid regions until now. We applied hybridization capture and shotgun sequencing to recover DNA sequences from bone specimens of ancient‐domestic dromedary ( Camelus dromedarius ) and its extinct ancestor, the wild dromedary from Jordan, Syria, Turkey and the Arabian Peninsula, respectively. Our results show that hybridization capture increased the percentage of mitochondrial DNA (mt DNA ) recovery by an average 187‐fold and in some cases yielded virtually complete mitochondrial (mt) genomes at multifold coverage in a single capture experiment. Furthermore, we tested the effect of hybridization temperature and time by using a touchdown approach on a limited number of samples. We observed no significant difference in the number of unique dromedary mt DNA reads retrieved with the standard capture compared to the touchdown method. In total, we obtained 14 partial mitochondrial genomes from ancient‐domestic dromedaries with 17–95% length coverage and 1.27–47.1‐fold read depths for the covered regions. Using whole‐genome shotgun sequencing, we successfully recovered endogenous dromedary nuclear DNA (nu DNA ) from domestic and wild dromedary specimens with 1–1.06‐fold read depths for covered regions. Our results highlight that despite recent methodological advances, obtaining ancient DNA ( aDNA ) from specimens recovered from hot, arid environments is still problematic. Hybridization protocols require specific optimization, and samples at the limit of DNA preservation need multiple replications of DNA extraction and hybridization capture as has been shown previously for Middle Pleistocene specimens.
On the Instrumentation of the Melody Line of Joseph Mysliveček's Symphonies Nos. 42-47
2016-06-11

Příspěvek se zabývá hudební analýzou melodických linií v Symfoniích č. 42-47 (ED. 10: D21, F8, Bb8, Eb6, G10 and C11) J. Myslivečka. Detailně jsou zkoumány následující aspekty: instrumentace basových linií, oktávová zdvojení melodie v rámci hudební věty, podíl smyčcových a žesťových nástrojů na provedení melodie. Symfonie jsou srovnávány s Myslivečkovou orchestrální operní hudbou ze stejného období, která využívá identickou instrumentaci, stejně tak s podobně instrumentovanými symfoniemi W. A Mozarta z období 1772-1774. Cílem komparace je určit společné jmenovatele děl obou tvůrců, dále definovat specifický kompoziční rukopis J. Myslivečka.
Neuronal Food Reward Activity in Patients With Type 2 Diabetes With Improved Glycemic Control After Bariatric Surgery
2016-06-12

OBJECTIVE Obesity and type 2 diabetes mellitus (T2DM) are associated with altered food-related neuronal functions. Besides weight loss, substantial improvement of glucose metabolism in patients with T2DM can be achieved by bariatric surgery. We aimed to target the neuronal and behavioral correlates of improved glycemic control after bariatric surgery. RESEARCH DESIGN AND METHODS Two patient groups with T2DM were recruited. The treatment group (n = 12) consisted of patients who had undergone Roux-en-Y gastric bypass (RYGB) surgery, and a control group consisted of patients who did not undergo surgery (n = 12). The groups were matched for age and current BMI. HbA1c was matched by using the presurgical HbA1c of the RYGB group and the current HbA1c of the nonsurgical group. Neuronal activation during a food reward task was measured using functional MRI (fMRI). Behavioral data were assessed through questionnaires. RESULTS RYGB improved HbA1c from 7.07 ± 0.50 to 5.70 ± 0.16% (P &amp;lt; 0.05) and BMI from 52.21 ± 1.90 to 35.71 ± 0.84 kg/m2 (P &amp;lt; 0.001). Behavioral results showed lower wanting and liking scores as well as lower eating behavior–related pathologies for the patients after RYGB than for similar obese subjects without surgery but with impaired glycemic control. The fMRI analysis showed higher activation for the nonsurgical group in areas associated with inhibition and reward as well as in the precuneus, a major connectivity hub in the brain. By contrast, patients after RYGB showed higher activation in the visual, motor, cognitive control, memory, and gustatory regions. CONCLUSIONS In obese patients with diabetes, RYGB normalizes glycemic control and leads to food reward–related brain activation patterns that are different from those of obese patients with less-well-controlled T2DM and without bariatric surgery. The differences in food reward processing might be one factor in determining the outcome of bariatric surgery in patients with T2DM.
Ceranib‐2‐induced suicidal erythrocyte death
2016-06-12

Ceramide is known to trigger apoptosis of nucleated cells and eryptosis of erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Besides ceramide, stimulators of eryptosis include increase of cytosolic Ca 2+ ‐activity ([Ca 2+ ] i ) and oxidative stress. Ceramide is degraded by acid ceramidase and inhibition of the enzyme similarly triggers apoptosis. The present study explored, whether ceramidase inhibitor Ceranib‐2 induces eryptosis. Flow cytometry was employed to quantify phosphatidylserine‐exposure at the cell surface from annexin‐V‐binding, cell volume from forward scatter, [Ca 2+ ] i from Fluo3‐fluorescence, reactive oxygen species (ROS) from DCF dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was estimated from hemoglobin concentration in the supernatant. A 48 h exposure of human erythrocytes to Ceranib‐2 significantly increased the percentage of annexin‐V‐binding cells (≥50 μM) and the percentage of hemolytic cells (≥10 μM) without significantly modifying forward scatter. Ceranib‐2 significantly increased Fluo3‐fluorescence, DCF fluorescence and ceramide abundance. The effect of Ceranib‐2 on annexin‐V‐binding was not significantly blunted by removal of extracellular Ca 2+ . Ceranib‐2 triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to increase of ceramide abundance and induction of oxidative stress, but not dependent on Ca 2+ entry. Copyright © 2016 John Wiley &amp; Sons, Ltd.
It’s About Connections – How the Economic Network of the German Federal Government Affects the Top Earners’ Average Income Tax Rate
2016-06-12

Abstract Building on arguments to political incomes, career concerns and elitist networks, this study assumes that an increasing percentage of highly incentivized former executive board members within the German Federal Government (1957–2012) will decrease the top earners’ average income tax rate during the subsequent year. Conversely, the percentage of lower incentivized former supervisory board members is assumed to increase the top earners’ average income tax rate. Both effects are assumed to be enforced if the ruling parties have strong support in the German Bundestag. The empirical results significantly confirm the unconditional effect for former executive board members and the conditional effect for former supervisory board members. Corresponding to sociological findings (see Hartmann 2002, Der Mythos von den Leistungseliten. Frankfurt a.M., Campus) and building on Barro’s (1973, The Control of Politicians: An Economic Model. Public Choice 14(1): 19–42) approach to the selfish maximization of political income and arguments regarding career concerns from principal agent theory (see, e. g. Fama 1980, Agency Problems and the Theory of the Firm. Journal of Political Economy 88, 288–307), this study assumes a strong incentive for former executive board members in the German Federal Government (1957–2012) to maximize their political income by lowering the top earners’ average income tax rate (1958–2013) due to their social elitist homogeneity and career concerns in terms of future job opportunities in business corporations. Conversely, former supervisory board members are assumed to increase the top earners’ average income tax rate due to their differing social backgrounds. Despite possible career concerns, they are assumed to increase the top earners’ average income tax rate in order not to lose their previously gained ideological credibility. Both effects are assumed to be enforced if the ruling parties have more than or equal to 55 % of seats in the German Bundestag. By running OLS and Tobit regressions, the empirical results confirm an unconditional decreasing effect of a higher percentage of previous executive board members and a conditional increasing effect of a higher percentage of previous supervisory board members on the top earners’ average income tax rate.
mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells
2016-06-13

Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR–dependent regulatory network for nutrient transport in renal proximal tubular cells.