julilili42/papers huggingface dataset:
Visual sensitivity under naturalistic viewing conditions
2014-08-22

Psychophysical experiments typically use very simple stimuli, such as isolated dots and gratings on uniform backgrounds, and allow no or only very stereotyped eye movements. While these viewing conditions are highly controllable, they are not representative of real-world vision, which is characterized by a complex, broadband input and several eye movements per second. We performed a series of experiments in which subjects freely watched high-resolution nature documentaries and TV shows on a gaze-contingent display. Eye-tracking at 1000 Hz and fast video processing routines allowed us to precisely modulate the stimulus in real time and in retinal coordinates. The task then was to locate either bandpass contrast changes or geometric distortions that briefly appeared in one of four locations relative to the fovea every few seconds. We confirm a well-known loss of sensitivity when video modulations took place around the time of eye movements, i.e. around episodes of high-speed retinal motion. However, we found that replicating the same retinal input in a passive condition, where subjects maintained central fixation and the video was shifted on the screen, led to a comparable loss in sensitivity. We conclude that no process of active, extra-retinal suppression is needed to explain peri-saccadic visual sensitivity under naturalistic conditions. We further find that the detection of spatial modifications depends on the spatio-temporal structure of the underlying scene, such that distortions are harder to detect in areas that vary rapidly across space or time. These results highlight the importance of naturalistic assessment for understanding visual processing. Meeting abstract presented at VSS 2014
Nephron sparing surgery (NSS) for unilateral wilms tumor (UWT): The SIOP 2001 experience
2014-08-23

Abstract Background Total nephrectomy (TN) remains the standard treatment of unilateral Wilms tumors (uWT). The SIOP WT‐2001 protocol allowed Nephron Sparing Surgery (NSS) for polar or peripherally non‐infiltrating tumors. Aim: Inventory of the current SIOP NSS‐experience. Procedures 2,800 patients with a unilateral, localized or metastatic and an unequivocal surgical technique recorded were included. All had neo‐adjuvant chemotherapy and delayed surgery. In 91 (3%) NSS was performed and in 2709 TN. Data was retrieved from the SIOP WT 2001 database. Results NSS group contained 65% stage I tumours and the TN group 48%. Tumor volume (at diagnosis and surgery) was significantly smaller in the NSS group. Within stage III, after NSS, 7/12 (58%) had positive margins (M + ) , 5 with tumor negative lymph nodes (LN‐). After TN, 355/712 (55%) had M + , 182 were LN‐. Treatment of M+ in the NSS group resulted in two conversions to TN (one combined with radiotherapy), three patients had radiotherapy only and in two patients local therapy, if given, was not recorded. After NSS, four recurrences occurred. For localized disease the 5‐year overall (OS) and event free survival (EFS) in NSS group was 100 and 94.8 (95% CI:89.9‐99.9), respectively, while OS and EFS in the TN group were 94.4 (95% CI: 93.2‐95.5, log‐rank test P = 0.06) and 86.5 (95% CI:85.0‐88.1, log‐rank test P = 0.06), respectively. Conclusions NSS was only performed in 3% of patients with uWT. Despite excellent survival with few relapses, the gain of nephrons needs to be weighed against the risk to induce stage III with intensified therapy. Pediatr Blood Cancer 2014;61:2175–2179. © 2014 Wiley Periodicals, Inc.
Therapeutic Molecules and Endogenous Ligands Regulate the Interaction between Brain Cellular Prion Protein (PrPC) and Metabotropic Glutamate Receptor 5 (mGluR5)
2014-08-23

Soluble Amyloid-β oligomers (Aβo) can trigger Alzheimer disease (AD) pathophysiology by binding to cell surface cellular prion protein (PrP(C)). PrP(C) interacts physically with metabotropic glutamate receptor 5 (mGluR5), and this interaction controls the transmission of neurotoxic signals to intracellular substrates. Because the interruption of the signal transduction from PrP(C) to mGluR5 has therapeutic potential for AD, we developed assays to explore the effect of endogenous ligands, agonists/antagonists, and antibodies on the interaction between PrP(C) and mGluR5 in cell lines and mouse brain. We show that the PrP(C) segment of amino acids 91-153 mediates the interaction with mGluR5. Agonists of mGluR5 increase the mGluR5-PrP(C) interaction, whereas mGluR5 antagonists suppress protein association. Synthetic Aβo promotes the protein interaction in mouse brain and transfected HEK-293 cell membrane preparations. The interaction of PrP(C) and mGluR5 is enhanced dramatically in the brains of familial AD transgenic model mice. In brain homogenates with Aβo, the interaction of PrP(C) and mGluR5 is reversed by mGluR5-directed antagonists or antibodies directed against the PrP(C) segment of amino acids 91-153. Silent allosteric modulators of mGluR5 do not alter Glu or basal mGluR5 activity, but they disrupt the Aβo-induced interaction of mGluR5 with PrP(C). The assays described here have the potential to identify and develop new compounds that inhibit the interaction of PrP(C) and mGluR5, which plays a pivotal role in the pathogenesis of Alzheimer disease by transmitting the signal from extracellular Aβo into the cytosol.
Epigenetic Impacts of Ascorbate on Human Metastatic Melanoma Cells
2014-08-25

In recent years, increasing evidence has emerged demonstrating that high-dose ascorbate bears cytotoxic effects on cancer cells in vitro and in vivo, making ascorbate a pro-oxidative drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. This anticancer effect of ascorbate is hypoxia-inducible factor-1α- and O2-dependent. However, whether the intracellular mechanisms governing this effect are modulated by epigenetic phenomena remains unknown. We treated human melanoma cells with physiological (200 μM) or pharmacological (8 mM) ascorbate for 1 h to record the impact on DNA methyltransferase (DNMT)-activity, histone deacetylases (HDACs), and microRNA (miRNA) expression after 12 h. The results were analyzed with the MIRUMIR online tool that estimates the power of miRNA to serve as potential biomarkers to predict survival of cancer patients. FACS cell-cycle analyses showed that 8 mM ascorbate shifted BLM melanoma cells toward the sub-G1 fraction starting at 12 h after an initial primary G2/M arrest, indicative for secondary apoptosis induction. In pharmacological doses, ascorbate inhibited the DNMT activity in nuclear extracts of MeWo and BLM melanoma cells, but did not inhibit human HDAC enzymes of classes I, II, and IV. The expression of 151 miRNAs was altered 12 h after ascorbate treatment of BLM cells in physiological or pharmacological doses. Pharmacological doses up-regulated 32 miRNAs (≥4-fold) mainly involved in tumor suppression and drug resistance in our preliminary miRNA screening array. The most prominently up-regulated miRNAs correlated with a significantly increased overall survival of breast cancer or nasopharyngeal carcinoma patients of the MIRUMIR database with high expression of the respective miRNA. Our results suggest a possible epigenetic signature of pharmacological doses of ascorbate in human melanoma cells and support further pre-clinical and possibly even clinical evaluation of ascorbate for melanoma therapy.
Sorption and transformation of the reactive tracers resazurin and resorufin in natural river sediments
2014-08-25

Abstract. Resazurin (Raz) and its reaction product resorufin (Rru) have increasingly been used as reactive tracers to quantify metabolic activity and hyporheic exchange in streams. Previous work has indicated that these compounds undergo sorption in stream sediments. We present laboratory experiments on Raz and Rru transport, sorption, and transformation, consisting of 4 column and 72 batch tests using 2 sediments with different physicochemical properties under neutral (pH = 7) and alkaline (pH = 9) conditions. The study aimed at identifying the key processes of reactive transport of Raz and Rru in streambed sediments and the experimental setup best suited for their determination. Data from column experiments were simulated by a travel-time-based model accounting for physical transport, equilibrium and kinetic sorption, and three first-order reactions. We derived the travel-time distributions directly from the breakthrough curve (BTC) of the conservative tracer, fluorescein, rather than from fitting an advective-dispersive transport model, and inferred from those distributions the transfer functions of Raz and Rru, which provided conclusive approximations of the measured BTCs. The most likely reactive transport parameters and their uncertainty were determined by a Markov chain–Monte Carlo approach. Sorption isotherms of both compounds were obtained from batch experiments. We found that kinetic sorption dominates sorption of both Raz and Rru, with characteristic timescales of sorption in the order of 12 to 298 min. Linear sorption models for both Raz and Rru appeared adequate for concentrations that are typically applied in field tracer tests. The proposed two-site sorption model helps to interpret transient tracer tests using the Raz–Rru system.
Fatty Acids as a Concept for Probes in Cardiologic PET/MR Imaging
2014-08-25

TO THE EDITOR: The June supplemental issue of The Journal of Nuclear Medicine reflects and enhances skillful developments in the merging of PET and MR imaging according to the existing status of qualified use. That, in particular, holds for cardiology, as Osman Ratib and René Nkoulou present
TAL effectors – pathogen strategies and plant resistance engineering
2014-08-26

Summary Transcription activator‐like effectors ( TALE s) from plant pathogenic Xanthomonas spp. and the related Rip TAL s from Ralstonia solanacearum are DNA ‐binding proteins with a modular DNA ‐binding domain. This domain is both predictable and programmable, which simplifies elucidation of TALE function in planta and facilitates generation of DNA ‐binding modules with desired specificity for biotechnological approaches. Recently identified TALE host target genes that either promote or stop bacterial disease provide new insights into how expression of TALE genes affects the plant–pathogen interaction. Since its elucidation the TALE code has been continuously refined and now provides a mature tool that, in combination with transcriptome profiling, allows rapid isolation of novel TALE target genes. The TALE code is also the basis for synthetic promoter‐traps that mediate recognition of TALE or Rip TAL proteins in engineered plants. In this review, we will summarize recent findings in plant‐focused TALE research. In addition, we will provide an outline of the newly established gene isolation approach for TALE or RipTAL host target genes with an emphasis on potential pitfalls.
Nontargeted Modification-Specific Metabolomics Study Based on Liquid Chromatography–High-Resolution Mass Spectrometry
2014-08-26

Modifications of genes and proteins have been extensively studied in systems biology using comprehensive analytical strategies. Although metabolites are frequently modified, these modifications have not been studied using -omics approaches. Here a general strategy for the nontargeted profiling of modified metabolites, which we call "nontargeted modification-specific metabolomics", is reported. A key aspect of this strategy was the combination of in-source collision-induced dissociation liquid chromatography-mass spectrometry (LC-MS) and global nontargeted LC-MS-based metabolomics. Characteristic neutral loss fragments that are specific for acetylation, sulfation, glucuronidation, glucosidation, or ribose conjugation were reproducibly detected using human urine as a model specimen for method development. The practical application of this method was demonstrated by profiling urine samples from liver cirrhosis patients. Approximately 900 features were identified as modified endogenous metabolites and xenobiotics. Moreover, this strategy supports the identification of compounds not included in traditional metabolomics databases (HMDB, Metlin, and KEGG), which are currently referred to as "unknowns" in metabolomics projects. Nontargeted modification-specific metabolomics opens a new perspective in systems biology.
NOD2 Stimulation by Staphylococcus aureus-Derived Peptidoglycan Is Boosted by Toll-Like Receptor 2 Costimulation with Lipoproteins in Dendritic Cells
2014-08-26

ABSTRACT Mutations in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) play an important role in the pathogenesis of Crohn's disease. NOD2 is an intracellular pattern recognition receptor (PRR) that senses bacterial peptidoglycan (PGN) structures, e.g., muramyl dipeptide (MDP). Here we focused on the effect of more-cross-linked, polymeric PGN fragments (PGNpol) in the activation of the innate immune system. In this study, the effect of combined NOD2 and Toll-like receptor 2 (TLR2) stimulation was examined compared to single stimulation of the NOD2 receptor alone. PGNpol species derived from a lipoprotein-containing Staphylococcus aureus strain (SA113) and a lipoprotein-deficient strain (SA113 Δ lgt ) were isolated. While PGNpol constitutes a combined NOD2 and TLR2 ligand, lipoprotein-deficient PGNpolΔ lgt leads to activation of the immune system only via the NOD2 receptor. Murine bone marrow-derived dendritic cells (BMDCs), J774 cells, and Mono Mac 6 (MM6) cells were stimulated with these ligands. Cytokines (interleukin-6 [IL-6], IL-12p40, and tumor necrosis factor alpha [TNF-α]) as well as DC activation and maturation parameters were measured. Stimulation with PGNpolΔ lgt did not lead to enhanced cytokine secretion or DC activation and maturation. However, stimulation with PGNpol led to strong cytokine secretion and subsequent DC maturation. These results were confirmed in MM6 and J774 cells. We showed that the NOD2-mediated activation of DCs with PGNpol was dependent on TLR2 costimulation. Therefore, signaling via both receptors leads to a more potent activation of the immune system than that with stimulation via each receptor alone.
Modulation of Amino Acid Metabolic Signatures by Supplemented Isoenergetic Diets Differing in Protein and Cereal Fiber Content
2014-08-26

We demonstrate that relatively short-term isoenergetic changes in the diet significantly alter the relation of AA signatures with IR, with possible implications on the determination and treatment of diabetes risk.
Drug and cell delivery for cardiac regeneration
2014-08-27

The spectrum of ischaemic cardiomyopathy, encompassing acute myocardial infarction to congestive heart failure is a significant clinical issue in the modern era. This group of diseases is an enormous source of morbidity and mortality and underlies significant healthcare costs worldwide. Cardiac regenerative therapy, whereby pro-regenerative cells, drugs or growth factors are administered to damaged and ischaemic myocardium has demonstrated significant potential, especially preclinically. While some of these strategies have demonstrated a measure of success in clinical trials, tangible clinical translation has been slow. To date, the majority of clinical studies and a significant number of preclinical studies have utilised relatively simple delivery methods for regenerative therapeutics, such as simple systemic administration or local injection in saline carrier vehicles. Here, we review cardiac regenerative strategies with a particular focus on advanced delivery concepts as a potential means to enhance treatment efficacy and tolerability and ultimately, clinical translation. These include (i) delivery of therapeutic agents in biomaterial carriers, (ii) nanoparticulate encapsulation, (iii) multimodal therapeutic strategies and (iv) localised, minimally invasive delivery via percutaneous transcatheter systems.
Binocular Glaucomatous Visual Field Loss and Its Impact on Visual Exploration - A Supermarket Study
2014-08-27

Advanced glaucomatous visual field loss may critically interfere with quality of life. The purpose of this study was to (i) assess the impact of binocular glaucomatous visual field loss on a supermarket search task as an example of everyday living activities, (ii) to identify factors influencing the performance, and (iii) to investigate the related compensatory mechanisms. Ten patients with binocular glaucoma (GP), and ten healthy-sighted control subjects (GC) were asked to collect twenty different products chosen randomly in two supermarket racks as quickly as possible. The task performance was rated as "passed" or "failed" with regard to the time per correctly collected item. Based on the performance of control subjects, the threshold value for failing the task was defined as μ+3σ (in seconds per correctly collected item). Eye movements were recorded by means of a mobile eye tracker. Eight out of ten patients with glaucoma and all control subjects passed the task. Patients who failed the task needed significantly longer time (111.47 s ±12.12 s) to complete the task than patients who passed (64.45 s ±13.36 s, t-test, p < 0.001). Furthermore, patients who passed the task showed a significantly higher number of glances towards the visual field defect (VFD) area than patients who failed (t-test, p < 0.05). According to these results, glaucoma patients with defects in the binocular visual field display on average longer search times in a naturalistic supermarket task. However, a considerable number of patients, who compensate by frequent glancing towards the VFD, showed successful task performance. Therefore, systematic exploration of the VFD area seems to be a "time-effective" compensatory mechanism during the present supermarket task.
Differential Regulation of Cone Calcium Signals by Different Horizontal Cell Feedback Mechanisms in the Mouse Retina
2014-08-27

Controlling neurotransmitter release by modulating the presynaptic calcium level is a key mechanism to ensure reliable signal transmission from one neuron to the next. In this study, we investigated how the glutamatergic output of cone photoreceptors (cones) in the mouse retina is shaped by different feedback mechanisms from postsynaptic GABAergic horizontal cells (HCs) using a combination of two-photon calcium imaging and pharmacology at the level of individual cone axon terminals. We provide evidence that hemichannel-mediated (putative ephaptic) feedback sets the cone output gain by defining the basal calcium level, a mechanism that may be crucial for adapting cones to the ambient light level. In contrast, pH-mediated feedback did not modulate the cone basal calcium level but affected the size and shape of light-evoked cone calcium signals in a contrast-dependent way: low-contrast light responses were amplified, whereas high-contrast light responses were reduced. Finally, we provide functional evidence that GABA shapes light-evoked calcium signals in cones. Because we could not localize ionotropic GABA receptors on cone axon terminals using electron microscopy, we suggest that GABA may act through GABA autoreceptors on HCs, thereby possibly modulating hemichannel- and/or pH-mediated feedback. Together, our results suggest that at the cone synapse, hemichannel-mediated (ephaptic) and pH-mediated feedback fulfill distinct functions to adjust the output of cones to changing ambient light levels and stimulus contrasts and that the efficacy of these feedback mechanisms is likely modulated by GABA release in the outer retina.
Task instructions modulate the attentional mode affecting the auditory MMN and the semantic N400
2014-08-27

Event-related potentials (ERPs) have been proven to be a useful tool to complement clinical assessment and to detect residual cognitive functions in patients with disorders of consciousness. These ERPs are often recorded using passive or unspecific instructions. Patient data obtained this way are then compared to data from healthy participants, which are usually recorded using active instructions. The present study investigates the effect of attentive modulations and particularly the effect of active vs. passive instruction on the ERP components mismatch negativity (MMN) and N400. A sample of 18 healthy participants listened to three auditory paradigms: an oddball, a word priming, and a sentence paradigm. Each paradigm was presented three times with different instructions: ignoring auditory stimuli, passive listening, and focused attention on the auditory stimuli. After each task, the participants indicated their subjective effort. The N400 decreased from the focused task to the passive task, and was extinct in the ignore task. The MMN exhibited higher amplitudes in the focused and passive task compared to the ignore task. The data indicate an effect of attention on the supratemporal component of the MMN. Subjective effort was equally high in the passive and focused tasks but reduced in the ignore task. We conclude that passive listening during EEG recording is stressful and attenuates ERPs, which renders the interpretation of the results obtained in such conditions difficult.
Coherent transport and symmetry breaking—laser dynamics of constrained granular matter
2014-08-27

We present diagrammatic transport theory including self-consistent nonlinear enhancement and dissipation in the multiple scattering regime. Our model of Vollhardt-W\\"olfle transport of photons is fit-parameter-free and raises the claim that the results hold up to the closest packed volume of randomly arranged ZnO Mie scatterers. We find that a symmetry breaking caused by dissipative effects of a lossy underlying substrate leads to qualitatively different physics of coherence and lasing in granular amplifying media. According to our results, confined and extended mode and their laser thresholds can be clearly attributed to unbroken and broken spatial symmetry. The diameters and emission profiles of random laser modes, as well as their thresholds and the positional-dependent degree of coherence can be checked experimentally.
Sham treatment shows similar effects on pain and function compared to a multimodal physiotherapeutic intervention programme in patients with painful hip osteoarthritis
2014-08-27

Commentary on : Bennell KL, Egerton T, Martin J, et al. Effect of physical therapy on pain and function in patients with hip osteoarthritis: a randomized clinical trial. JAMA 2014;311:1987–97.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Despite an increasing body of evidence for the efficacy of exercise and manual therapy in the treatment of hip osteoarthritis, there are relatively few evaluations of multimodal physical therapy regimes.1 ,2 The same is true for the comparison of physical therapy with sham treatment, as most interventions are compared to general practitioner care or untreated control. The primary aim of this study therefore, was to test the hypothesis that a 12-week multimodal physical therapy programme has a superior treatment effect in comparison with sham treatment in patients with hip osteoarthritis. A randomised controlled trial (RCT) was conducted to ... [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.volume%253D311%26rft.spage%253D1987%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.2014.4591%26rft_id%253Dinfo%253Apmid%252F24846036%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.2014.4591&link_type=DOI [3]: /lookup/external-ref?access_num=24846036&link_type=MED&atom=%2Febmed%2F19%2F6%2F216.atom [4]: /lookup/external-ref?access_num=000336122800021&link_type=ISI