julilili42/papers huggingface dataset:
TBAI-Catalyzed Oxidative Cross-Coupling of Phenols and 2-Aminoacetophenones
2015-03-12

An iodide-catalyzed oxidative cross-coupling between phenols and 2-aminoacetophenones has been developed. Using catalytic amounts of tetrabutylammoniumiodide (TBAI) as an iodine-containing catalyst and aqueous solutions of tert-butyl hydro-peroxide (TBHP) as the stoichiometric co-oxidant, a variety of α-phenoxylated 2-aminoacetophenones could be obtained in yields of up to 92% after remarkably short reaction times (20 min). This is a very rare example for an iodide-catalyzed intermolecular cross-coupling utilizing phenols. However, this efficient methodology could be further extended toward an intramolecular variant which gives direct access to a range of dihydro-4H-benzo[e][1,3]oxazin-4-ones.
Shine-Through in PET/MR Imaging: Effects of the Magnetic Field on Positron Range and Subsequent Image Artifacts
2015-03-12

In simultaneous PET/MR imaging, the effect of the magnetic field on positrons may cause severe artifacts in the PET image when the lesions are close to air cavities and high-energy radioisotopes are used. For accurate staging and interpretation, this effect needs to be recognized and adequate compensation techniques should be developed.
η3‐Allyl Coordination at Tin(II)—Reactivity towards Alkynes and Benzonitrile
2015-03-12

Abstract We herein report the synthesis and characterization of a terphenyl‐substituted Sn II allyl compound featuring an η 3 coordination mode in solution and in the solid state. Two examples for the interesting reactivity of the allyl Sn II molecule are presented: Reactions with terminal alkynes result in the formation of tricyclic compounds by CC bond formation and the dimerization of two Sn moieties whereas the reaction with benzonitrile leads to a sixteen‐membered ring system through CH activation.
Influence of the β2-Subunit of L-Type Voltage-Gated Cav Channels on the Structural and Functional Development of Photoreceptor Ribbon Synapses
2015-03-12

The presence of the Cavβ2 is essential for the structural integrity and function of the rod photoreceptor synapse. The Cavβ2 is less essential for the morphology of cone and bipolar cell ribbon synapses, although the impaired photopic electroretinogram suggests a functional alteration also of the cone-mediated signaling in Cavβ2-deficient retinas.
Report onDrosophila melanogasterlarvae without functional tracheae
2015-03-12

Abstract A network of tubes, the tracheal system, ensures circulation of oxygen and carbon dioxide in insects. A stabilizing chitinous cuticle lines this ectodermal tissue that commonly fills with gas shortly before hatching. In this study, we report on D rosophila melanogaster larvae that lack a functional tracheal system through the reduction of the expression of the cuticle gene kkv or snsl by specific RNA interference in tracheal cells of the embryo. These embryos complete development and hatch arguing that functional tracheae are not required for embryogenesis. After hatching, larvae with dysfunctional tracheae ingest only little food and grow slowly. Without attaining the critical size for stage transition, a few of them moult to the next larval stage. We further show that hypoxia is induced in these larvae that conceptually switch to skin respiration. The rescue response is, however, futile and the respective larvae die latest after 4 days. Hence, a small body size and skin respiration per se are insufficient to ensure survival. Based on our data, we hypothesize that a low oxygen concentration entails a conflict between the developmental progress and a protective programme destined to restrict growth under hypoxia. D . melanogaster larvae with dysfunctional tracheae will be useful to identify those factors accounting for the impact of respiration on growth and development ultimately allowing understanding these aspects of insect ecology.
The ubiquitin-specific peptidase 8 (USP8) gene is frequently mutated in adenomas causing Cushing's disease.
2015-03-12

[08:00 – 08:10]We have recently reported that somatic mutations in the ubiquitin-specific peptidase USP8 are present in corticotropinomas of patients with Cushing's disease and that these mutations reduced the interaction with 14 – 3-3. Mutant USP8 exhibited higher deubiquitination activity and promoted POMC expression in an EGFR-depending fashion (Reincke et al., Nat. Genetics 2014). To further study the prevalence of these mutations, we have analyzed 145 ACTH-producing corticotropinomas of patients with diagnosed Cushing's disease from 8 different centers by Sanger sequencing.
Managing Expectations When Publishing Tools and Methods for Computational Proteomics
2015-03-12

Computational tools are pivotal in proteomics because they are crucial for identification, quantification, and statistical assessment of data. The gateway to finding the best choice of a tool or approach for a particular problem is frequently journal articles, yet there is often an overwhelming variety of options that makes it hard to decide on the best solution. This is particularly difficult for nonexperts in bioinformatics. The maturity, reliability, and performance of tools can vary widely because publications may appear at different stages of development. A novel idea might merit early publication despite only offering proof-of-principle, while it may take years before a tool can be considered mature, and by that time it might be difficult for a new publication to be accepted because of a perceived lack of novelty. After discussions with members of the computational mass spectrometry community, we describe here proposed recommendations for organization of informatics manuscripts as a way to set the expectations of readers (and reviewers) through three different manuscript types that are based on existing journal designations. Brief Communications are short reports describing novel computational approaches where the implementation is not necessarily production-ready. Research Articles present both a novel idea and mature implementation that has been suitably benchmarked. Application Notes focus on a mature and tested tool or concept and need not be novel but should offer advancement from improved quality, ease of use, and/or implementation. Organizing computational proteomics contributions into these three manuscript types will facilitate the review process and will also enable readers to identify the maturity and applicability of the tool for their own workflows.
KI-67 labeling index and expression of P53 are non-predictive on invasiveness and tumour size in functional and nonfunctional pituitary adenomas: A large series of 421 patients
2015-03-12

Introduction: The nuclear protein KI-67 is a marker for cellular proliferation and its expression level correlates significantly with tumour growth rate of pituitary adenomas. Together with excessive p53 activity, atypical adenomas are defined by a KI-67 labeling index (LI) > 3%. Nevertheless it is still controversially discussed whether an increased proliferation index is correlated with the tumour invasiveness, which is a major criteria for operability and long-term remission after surgery. In this large monocentric case study we investigated the correlation between the proliferation indices (KI-67 and p53 expression levels) and invasiveness and size of pituitary adenomas.
Intranasally administered Orexin-A does not activate sympathetic baroreflex function in healthy humans
2015-03-12

Background: Orexin-A is a hypothalamic hormone crucially involved in the regulation of sleep/wake states. Orexin-A was previously reported to induce blood pressure (BP) relevant sympathetic activation in animals and orexin-neurons were shown to project towards BP regulating brain structures. In humans intranasal (i.n.) administration has been shown to effectively deliver neuropeptides directly to the central nervous system. In human narcolepsy, a disorder characterized by deficient orexin-A signalling, i.n. orexin-A provided functional effects of sleep architecture. However, sympathetic blood pressure effects remain to be elucidated. Using highly specific microneurographic techniques we investigated, whether i.n. orexin-A would alter sympathetic baroreflex function in healthy humans.
Polygenic risk of Parkinson disease is correlated with disease age at onset
2015-03-13

Objective We have investigated the polygenic architecture of Parkinson disease (PD) and have also explored the potential relationship between an individual's polygenic risk score and their disease age at onset. Methods This study used genotypic data from 4,294 cases and 10,340 controls obtained from the meta‐analysis of PD genome‐wide association studies. Polygenic score analysis was performed as previously described by the International Schizophrenia Consortium, testing whether the polygenic score alleles identified in 1 association study were significantly enriched in the cases relative to the controls of 3 independent studies. Linear regression was used to investigate the relationship between an individual's polygenic score for PD risk alleles and disease age at onset. Results Our polygenic score analysis has identified significant evidence for a polygenic component enriched in the cases of each of 3 independent PD genome‐wide association cohorts (minimum p = 3.76 × 10 −6 ). Further analysis identified compelling evidence that the average polygenic score in patients with an early disease age at onset was significantly higher than in those with a late age at onset ( p = 0.00014). Interpretation This provides strong support for a large polygenic contribution to the overall heritable risk of PD and also suggests that early onset forms of the illness are not exclusively caused by highly penetrant Mendelian mutations, but can also be contributed to by an accumulation of common polygenic alleles with relatively low effect sizes. Ann Neurol 2015;77:582–591
Nitrogen Starvation Acclimation in Synechococcus elongatus: Redox-Control and the Role of Nitrate Reduction as an Electron Sink
2015-03-13

Nitrogen starvation acclimation in non-diazotrophic cyanobacteria is characterized by a process termed chlorosis, where the light harvesting pigments are degraded and the cells gradually tune down photosynthetic and metabolic activities. The chlorosis response is governed by a complex and poorly understood regulatory network, which converges at the expression of the nblA gene, the triggering factor for phycobiliprotein degradation. This study established a method that allows uncoupling metabolic and redox-signals involved in nitrogen-starvation acclimation. Inhibition of glutamine synthetase (GS) by a precise dosage of l-methionine-sulfoximine (MSX) mimics the metabolic situation of nitrogen starvation. Addition of nitrate to such MSX-inhibited cells eliminates the associated redox-stress by enabling electron flow towards nitrate/nitrite reduction and thereby, prevents the induction of nblA expression and the associated chlorosis response. This study demonstrates that nitrogen starvation is perceived not only through metabolic signals, but requires a redox signal indicating over-reduction of PSI-reduced electron acceptors. It further establishes a cryptic role of nitrate/nitrite reductases as electron sinks to balance conditions of over-reduction.
FTIR Study of the Impact of PC[60]BM on the Photodegradation of the Low Band Gap Polymer PCPDTBT under O2 Environment
2015-03-13

The photodegradation of the low band gap polymer poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT) during irradiation under white light (AM 1.5 conditions) has been studied in pristine polymer films as well as in blend films with [6,6]-phenyl C61 butyric acid methyl ester (PC[60]BM). In order to gain insight into the degradation process, FTIR spectroscopy has been used to follow the evolution of different subunits of the polymer and to probe the chemical product formation. In contrast to other polymers, not the alkyl side chains but the π-conjugated system is preferentially oxidized during the first stages of degradation. Furthermore, it has been shown that the subunits of the polymer backbone are differently affected by the degradation. Blending the polymer with PC[60]BM leads to a significantly larger impact on the stability of the cyclopentadiene group compared to the benzene ring of the benzothiadiazole group.
Semi-Quantitative vs. Volumetric Determination of Endolymphatic Space in Menière’s Disease Using Endolymphatic Hydrops 3T-HR-MRI after Intravenous Gadolinium Injection
2015-03-13

Magnetic resonance imaging enhances the clinical diagnosis of Menière's disease. This is accomplished by in vivo detection of endolymphatic hydrops, which are graded using different semi-quantitative grading systems. We evaluated an established, semi-quantitative endolymphatic hydrops score and with a quantitative method for volumetric assessment of the endolymphatic size. 11 patients with Menière's disease and 2 healthy subjects underwent high resolution endolymphatic hydrops 3 Tesla MRI with highly T2 weighted FLAIR and T2DRIVE sequences. The degree of endolymphatic hydrops was rated semi-quantitatively and compared to the results of 3D-volumetry. Moreover, the grade of endolymphatic hydrops was correlated with pure tone audiometry. Semi-quantitative grading and volumetric evaluation of the endolymphatic hydrops are in accordance (r = 0.92) and the grade of endolymphatic hydrops correlates with pure tone audiometry. Patients with a sickness duration of ≥ 30 months showed a significant higher total labyrinth fluid volume (p = 0.03). Fast, semi-quantitative evaluation of endolymphatic hydrops is highly reliable compared to quantitative/volumetric assessment. Endolymphatic space is significantly higher in patients with longer sickness duration.
On the Significance of Bodily Awareness for Bodily Action: Figure 1.
2015-03-13

What is the significance of bodily awareness for bodily action? The orthodox philosophical account from O'Shaughnessy claims that bodily awareness is necessary for bodily action. Whilst O'Shaughnessy's account appears to be consonant with the phenomenology of ordinary agency, it falls afoul to empirical counterexamples. The failure of O'Shaughnessy's account and its cousins might suggest that bodily action does not depend on bodily awareness. On the contrary, I argue that the contrast between the character of afferented and deafferented agency shows that bodily awareness is crucial to explaining the distinctive character of bodily action in neurologically normal agents. In particular, the capacity to feel one's body 'from the inside' appears to be a condition on the capacity to act with one's body in a way that is not like remote control. This dependency of capacities is at once empirically adequate and in tune with the phenomenology of ordinary agency.
Crystal Structure of the N-Acetylmuramic Acid α-1-Phosphate (MurNAc-α1-P) Uridylyltransferase MurU, a Minimal Sugar Nucleotidyltransferase and Potential Drug Target Enzyme in Gram-negative Pathogens
2015-03-13

The N-acetylmuramic acid α-1-phosphate (MurNAc-α1-P) uridylyltransferase MurU catalyzes the synthesis of uridine diphosphate (UDP)-MurNAc, a crucial precursor of the bacterial peptidoglycan cell wall. MurU is part of a recently identified cell wall recycling pathway in Gram-negative bacteria that bypasses the general de novo biosynthesis of UDP-MurNAc and contributes to high intrinsic resistance to the antibiotic fosfomycin, which targets UDP-MurNAc de novo biosynthesis. To provide insights into substrate binding and specificity, we solved crystal structures of MurU of Pseudomonas putida in native and ligand-bound states at high resolution. With the help of these structures, critical enzyme-substrate interactions were identified that enable tight binding of MurNAc-α1-P to the active site of MurU. The MurU structures define a "minimal domain" required for general nucleotidyltransferase activity. They furthermore provide a structural basis for the chemical design of inhibitors of MurU that could serve as novel drugs in combination therapy against multidrug-resistant Gram-negative pathogens.
Evaluation of preparation methods for MS‐based analysis of intestinal epithelial cell proteomes
2015-03-13

The gut epithelium formed between an organism and the environment plays an essential role in host–microbe interactions, yet remains one of the least characterized mammalian tissues. Especially the membrane proteins, which are critical to bacterial adhesion, are understudied, because these proteins are low in abundance, and large amounts of sample is needed for their preparation and for undertaking MS‐based analysis. The aim of this study was to evaluate three different methods for isolation and preparation of pig intestinal epithelial cells for MS‐based analysis of the proteome. Samples were analyzed by LC and electrospray QTOF‐MS. The methods were evaluated according to efficiency, purity, transmembrane protein recovery, as well as for suitability to large‐scale preparations. Our data clearly demonstrate that mucosal shaving is by far the best‐suited method for in‐depth MS analysis in terms of ease and speed of sample preparation, as well as protein recovery. In comparison, more gentle methods where intestinal epithelial cells are harvested by shaking are more time consuming, result in lower protein yield, and are prone to increased technical variation due to multiple steps involved.
Eight thousand years of natural selection in Europe
2015-03-14

The arrival of farming in Europe around 8,500 years ago necessitated adaptation to new environments, pathogens, diets, and social organizations. While indirect evidence of adaptation can be detected in patterns of genetic variation in present-day people, ancient DNA makes it possible to witness selection directly by analyzing samples from populations before, during and after adaptation events. Here we report the first genome-wide scan for selection using ancient DNA, capitalizing on the largest genome-wide dataset yet assembled: 230 West Eurasians dating to between 6500 and 1000 BCE, including 163 with newly reported data. The new samples include the first genome-wide data from the Anatolian Neolithic culture, who we show were members of the population that was the source of Europe’s first farmers, and whose genetic material we extracted by focusing on the DNA-rich petrous bone. We identify genome-wide significant signatures of selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.
Chorein addiction in VPS13A overexpressing rhabdomyosarcoma cells
2015-03-14

Chorein encoded by VPS13A (vacuolar protein sorting-associated protein 13A) is defective in chorea-acanthocytosis. Chorein fosters neuronal cell survival, cortical actin polymerization and cell stiffness. In view of its anti-apoptotic effect in neurons, we explored whether chorein is expressed in cancer cells and influences cancer cell survival. RT-PCR was employed to determine transcript levels, specific siRNA to silence chorein, FACS analysis to follow apoptosis and Western blotting to quantify protein abundance. Chorein transcripts were detected in various cancer cell types. The mRNA coding for chorein and chorein protein were most abundant in drug resistant, poorly differentiated human rhabdomyosarcoma cells. Chorein silencing significantly reduced the ratio of phosphorylated (and thus activated) to total phosphoinositide 3 kinase (PI-3K), pointing to inactivation of this crucial pro-survival signaling molecule. Moreover, chorein silencing diminished transcript levels and protein expression of anti-apoptotic BCL-2 and enhanced transcript levels of pro-apoptotic Bax. Silencing of chorein in rhabdomyosarcoma cells was followed by mitochondrial depolarization, caspase 3 activation and stimulation of early and late apoptosis. In conclusion, chorein is expressed in various cancer cells. In cells with high chorein expression levels chorein silencing promotes apoptotic cell death, an effect paralleled by down-regulation of PI-3K activity and BCL-2/Bax expression ratio.
Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles
2015-03-16

Significance By imaging cyclic GMP (cGMP) in live ovarian follicles from mice, we show how luteinizing hormone signaling in the follicle periphery results in a rapid decrease in cGMP in the oocyte, thus reinitiating meiosis. Luteinizing hormone signaling lowers cGMP in the outer cells of the follicle, then cGMP in the oocyte decreases as a consequence of diffusion through gap junctions. These findings demonstrate directly that a physiological signal initiated by a stimulus in one region of an intact tissue can travel across many layers of cells via cyclic nucleotide diffusion through gap junctions.
Understanding the Structure–Function Relationship of Lysozyme Resistance in Staphylococcus aureus by Peptidoglycan O-Acetylation Using Molecular Docking, Dynamics, and Lysis Assay
2015-03-16

Lysozyme is an important component of the host innate defense system. It cleaves the β-1,4 glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine of bacterial peptidoglycan and induce bacterial lysis. Staphylococcus aureus (S. aureus), an opportunistic commensal pathogen, is highly resistant to lysozyme, because of the O-acetylation of peptidoglycan by O-acetyl transferase (oatA). To understand the structure-function relationship of lysozyme resistance in S. aureus by peptidoglycan O-acetylation, we adapted an integrated approach to (i) understand the effect of lysozyme on the growth of S. aureus parental and the oatA mutant strain, (ii) study the lysozyme induced lysis of exponentially grown and stationary phase of both the S. aureus parental and oatA mutant strain, (iii) investigate the dynamic interaction mechanism between normal (de-O-acetylated) and O-acetylated peptidoglycan substrate in complex with lysozyme using molecular docking and molecular dynamics simulations, and (iv) quantify lysozyme resistance of S. aureus parental and the oatA mutant in different human biological fluids. The results indicated for the first time that the active site cleft of lysozyme binding with O-acetylated peptidoglycan in S. aureus was sterically hindered and the structural stability was higher for the lysozyme in complex with normal peptidoglycan. This could have conferred reduced survival of the S. aureus oatA mutant in different human biological fluids. Consistent with this computational analysis, the experimental data confirmed decrease in the growth, lysozyme induced lysis, and lysozyme resistance, due to peptidoglycan O-acetylation in S. aureus.
Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine
2015-03-16

Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted.