julilili42/papers huggingface dataset:
New Aminocoumarins from the Rare Actinomycete Catenulispora acidiphila DSM 44928: Identification, Structure Elucidation, and Heterologous Production
2014-02-19

Abstract Genome mining led to the discovery of a novel aminocoumarin gene cluster in the rare actinomycete Catenulispora acidiphila DSM 44928. Sequence analysis revealed the presence of genes putatively involved in export/resistance, regulation, and biosynthesis of the aminocoumarin moiety and its halogenation, as well as several genes with so far unknown function. Two new aminocoumarins, cacibiocin A and B, were identified in the culture broth of C. acidiphila . Heterologous expression of the putative gene cluster in Streptomyces coelicolor M1152 confirmed that this cluster is responsible for cacibiocin biosynthesis. Furthermore, total production levels of cacibiocins could be increased by heterologous expression and screening of different culture media from an initial yield of 4.9 mg L −1 in C. acidiphila to 60 mg L −1 in S. coelicolor M1152. By HR‐MS and NMR analysis, cacibiocin A was found to contain a 3‐amino‐4,7‐dihydroxycoumarin moiety linked by an amide bond to a pyrrole‐2,5‐dicarboxylic acid. The latter structural motif has not been identified previously in any natural compound. Additionally, cacibiocin B contains two chlorine atoms at positions 6′ and 8′ of the aminocoumarin moiety.
Proteomic Survey Reveals Altered Energetic Patterns and Metabolic Failure Prior to Retinal Degeneration
2014-02-19

Inherited mutations that lead to misfolding of the visual pigment rhodopsin (Rho) are a prominent cause of photoreceptor neuron (PN) degeneration and blindness. How Rho proteotoxic stress progressively impairs PN viability remains unknown. To identify the pathways that mediate Rho toxicity in PNs, we performed a comprehensive proteomic profiling of retinas from Drosophila transgenics expressing Rh1 P37H , the equivalent of mammalian Rho P23H , the most common Rho mutation linked to blindness in humans. Profiling of young Rh1 P37H retinas revealed a coordinated upregulation of energy-producing pathways and attenuation of energy-consuming pathways involving target of rapamycin (TOR) signaling, which was reversed in older retinas at the onset of PN degeneration. We probed the relevance of these metabolic changes to PN survival by using a combination of pharmacological and genetic approaches. Chronic suppression of TOR signaling, using the inhibitor rapamycin, strongly mitigated PN degeneration, indicating that TOR signaling activation by chronic Rh1 P37H proteotoxic stress is deleterious for PNs. Genetic inactivation of the endoplasmic reticulum stress-induced JNK/TRAF1 axis as well as the APAF-1/caspase-9 axis, activated by damaged mitochondria, dramatically suppressed Rh1 P37H -induced PN degeneration, identifying the mitochondria as novel mediators of Rh1 P37H toxicity. We thus propose that chronic Rh1 P37H proteotoxic stress distorts the energetic profile of PNs leading to metabolic imbalance, mitochondrial failure, and PN degeneration and therapies normalizing metabolic function might be used to alleviate Rh1 P37H toxicity in the retina. Our study offers a glimpse into the intricate higher order interactions that underlie PN dysfunction and provides a useful resource for identifying other molecular networks that mediate Rho toxicity in PNs.
Synchrotron-Based Chemical Nano-Tomography of Microbial Cell-Mineral Aggregates in their Natural, Hydrated State
2014-02-19

Abstract Chemical nano-tomography of microbial cells in their natural, hydrated state provides direct evidence of metabolic and chemical processes. Cells of the nitrate-reducing Acidovorax sp. strain BoFeN1 were cultured in the presence of ferrous iron. Bacterial reduction of nitrate causes precipitation of Fe(III)-(oxyhydr)oxides in the periplasm and in direct vicinity of the cells. Nanoliter aliquots of cell-suspension were injected into custom-designed sample holders wherein polyimide membranes collapse around the cells by capillary forces. The immobilized, hydrated cells were analyzed by synchrotron-based scanning transmission X-ray microscopy in combination with angle-scan tomography. This approach provides three-dimensional (3D) maps of the chemical species in the sample by employing their intrinsic near-edge X-ray absorption properties. The cells were scanned through the focus of a monochromatic soft X-ray beam at different, chemically specific X-ray energies to acquire projection images of their corresponding X-ray absorbance. Based on these images, chemical composition maps were then calculated. Acquiring projections at different tilt angles allowed for 3D reconstruction of the chemical composition. Our approach allows for 3D chemical mapping of hydrated samples and thus provides direct evidence for the localization of metabolic and chemical processes in situ .
Interplay between Endothelin and Erythropoietin in Astroglia: The Role in Protection against Hypoxia
2014-02-19

We show that, under in vitro conditions, the vulnerability of astroglia to hypoxia is reflected by alterations in endothelin (ET)-1 release and capacity of erythropoietin (EPO) to regulate ET-1 levels. Exposure of cells to 24 h hypoxia did not induce changes in ET-1 release, while 48–72 h hypoxia resulted in increase of ET-1 release from astrocytes that could be abolished by EPO. The endothelin receptor type A (ETA) antagonist BQ123 increased extracellular levels of ET-1 in human fetal astroglial cell line (SV-FHAS). The survival and proliferation of rat primary astrocytes, neural precursors, and neurons upon hypoxic conditions were increased upon administration of BQ123. Hypoxic injury and aging affected the interaction between the EPO and ET systems. Under hypoxia EPO decreased ET-1 release from astrocytes, while ETA receptor blockade enhanced the expression of EPO mRNA and EPO receptor in culture-aged rat astroglia. The blockade of ETA receptor can increase the availability of ET-1 to the ETB receptor and can potentiate the neuroprotective effects of EPO. Thus, the new therapeutic use of combined administration of EPO and ETA receptor antagonists during hypoxia-associated neurodegenerative disorders of the central nervous system (CNS) can be suggested.
Differential ability to resist to complement lysis and invade host cells mediated by MBL in R4 and 860 strains of Trypanosoma cruzi
2014-02-19

To produce an infection Trypanosoma cruzi must evade lysis by the complement system. During early stages of infection, the lectin pathway plays an important role in host defense and can be activated by binding of mannan‐binding lectin (MBL) to carbohydrates on the surface of pathogens. We hypothesized that MBL has a dual role during parasite‐host cell interaction as lectin complement pathway activator and as binding molecule to invade the host cell. We used two polarized strains of T. cruzi , R4 (susceptible) and 860 (resistant) strains, to investigate the role of MBL in complement‐mediated lysis. Interestingly R4, but not 860 metacyclic strain, markedly increases the invasion of host cells, suggesting that MBL drives the invasion process while the parasite deactivates the Lectin complement pathway.
Tournament Structures in Japan and the U.S. : Why are They Different and Will they Change?
2014-02-19

Organizational reward systems based on rank order tournaments are used throughout the world. Still, the tournamentstructures applied in different countries differ substantially: While in the U.S., promotion tournaments are the mostprominent, Japanese organizations predominantly make use of bonus payment tournaments. In our paper, we askwhy tournament structures might have evolved so differently in the two countries. Referring to recent advances intournament theory showing that Japanese bonus payment tournaments dominate U.S. type promotion tournaments ifemployees are sufficiently risk-averse, we search for evidence that might hint at a higher degree of risk-aversion ofJapanese as opposed to U.S. employees. Having identified cultural as well as institutional factors that indeed mightfoster a higher degree of risk aversion on the part of Japanese employees, we render one potential explanation whytournament structures in Japan differ from those in the U.S.. To the extent that institutional factors are currentlychanging in Japan, we expect to observe changes in tournament structures as well. We conclude by discussing therecent changes in Japanese institutions and culture and their potential implications for the future use of tournamentstructures.
Optical near-fields & nearfield optics
2014-02-19

Optical methods provide exceedingly powerful tools in science and technology for measuring, analyzing and manipulating, from optical microscopy and spectroscopy to the characterization of ultrafast processes by femtosecond pulses and the modification of materials by intense laser radiation. However, when it comes to applications in the nanometer-regime, the conventional optical techniques suffer from the resolution limit – formulated by Ernst Abbe one and a half centuries ago – that light cannot be focused to a diameter much less than half its wavelength. This seems like a serious drawback for the use of optics in nanoscience and nanotechnology, since many of the nanostructures of interest are distinctly smaller than this limit of a few hundred nanometers. Fortunately, this restriction can be overcome, if one does not rely on focusing with lenses and mirrors in the optical far-field, but rather exploits the optical near-field in the vicinity of nanostructures. In this Thematic Series, various examples for the use of optical near-fields and near-field optics are presented.
Improved Lanthipeptide Detection and Prediction for antiSMASH
2014-02-20

Lanthipeptides are a class of ribosomally synthesised and post-translationally modified peptide (RiPP) natural products from the bacterial secondary metabolism. Their name is derived from the characteristic lanthionine or methyl-lanthionine residues contained in the processed peptide. Lanthipeptides that possess an antibacterial activity are called lantibiotics. Whereas multiple tools exist to identify lanthipeptide gene clusters from genomic data, no programs are available to predict the post-translational modifications of lanthipeptides, such as the proteolytic cleavage of the leader peptide part or tailoring modifications based on the analysis of the gene cluster sequence. antiSMASH is a software pipeline for the identification of secondary metabolite biosynthetic clusters from genomic input and the prediction of products produced by the identified clusters. Here we present a novel antiSMASH module using a rule-based approach to combine signature motifs for biosynthetic enzymes and lanthipeptide-specific cleavage site motifs to identify lanthipeptide clusters in genomic data, assign the specific lanthipeptide class, predict prepeptide cleavage, tailoring reactions, and the processed molecular weight of the mature peptide products.
Health, Dietary Habits, and Achievement Motivation in College Students With Self-Reported ADHD Diagnosis
2014-02-20

Objective: The present study aimed to investigate aspects of health and motivation in a subpopulation of college students with ADHD. Method: Seventy-seven college students with self-reported ADHD (49 women; M age = 25.82, SD = 4.62) and 120 college students without ADHD (65 women; M age = 25.17, SD = 5.41) participated in an online survey assessing their health, dietary habits, and achievement motivation. Results: College students with ADHD showed impairment in psychological functioning, impairment in their mental health, and reported more ambition and less self-control. Furthermore, we found gender differences: Women with ADHD reported worse psychological functioning, and the gender differences in obsessive-compulsive behavior and compensatory effort were mediated by the timing of diagnosis. Conclusion: College students, especially women, with ADHD struggle with health-related issues. Some of these gender differences might be due to under diagnosis of girls in childhood. Differences in achievement motivation might indicate compensatory mechanisms.
Acquisition of Comparison Constructions
2014-02-20

This article presents a study on the time course of the acquisition of comparison constructions. The order in which comparison constructions (comparatives, measure phrases, superlatives, degree questions, etc.) show up in English- and German-learning children's spontaneous speech is quite fixed. It is shown to be insufficiently determined by factors like frequency. Instead, a model of parametric variation in the grammar of comparison is shown to predict the order we observe.
Breakdown of Phosphatidylserine Asymmetry Following Treatment of Erythrocytes with Lumefantrine
2014-02-20

Background: Lumefantrine, a commonly used antimalarial drug, inhibits hemozoin formation in parasites. Several other antimalarial substances counteract parasitemia by triggering suicidal death or eryptosis of infected erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i), formation of ceramide, oxidative stress and/or activation of p38 kinase, protein kinase C (PKC), or caspases. The present study explored, whether lumefantrine stimulates eryptosis. Methods: Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species from 2',7'-dichlorodihydrofluorescein-diacetate fluorescence, content of reduced glutathione (GSH) from mercury orange fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 h exposure to lumefantrine (3 μg/mL) was followed by a significant increase of annexin-V-binding without significantly altering forward scatter, [Ca2+]i, ROS formation, reduced GSH, or ceramide abundance. The annexin-V-binding following lumefantrine treatment was not significantly modified by p38 kinase inhibitors SB203580 (2 μM) and p38 Inh III (1 μM), PKC inhibitor staurosporine (1 μM) or pancaspase inhibitor zVAD (1 or 10 μM). Conclusions: Lumefantrine triggers cell membrane scrambling, an effect independent from entry of extracellular Ca2+, ceramide formation, ROS formation, glutathione content, p38 kinase, PKC or caspases.
Comparable Autoantibody Serum Levels against Amyloid- and Inflammation-Associated Proteins in Parkinson’s Disease Patients and Controls
2014-02-21

Naturally occurring autoantibodies (NAbs) against a number of potentially disease-associated cellular proteins, including Amyloid-beta1-42 (Abeta1-42), Alpha-synuclein (Asyn), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and S100 calcium binding protein B (S100B) have been suggested to be associated with neurodegenerative disorders, in particular Alzheimer's (AD) and Parkinson's disease (PD). Whereas the (reduced) occurrence of specific NAbs in AD is widely accepted, previous literature examining the relation of these NAb titres between PD patients and controls, as well as comparing these levels with demographic and clinical parameters in PD patients have produced inconsistent findings. We therefore aimed, in a cross-sectional approach, to determine serum titres of the above NAbs in a cohort of 93 PD patients (31 of them demented) and 194 controls. Levels were correlated with demographic and clinical variables, cerebrospinal fluid Abeta1-42, total tau and phospho-tau levels, as well as with single nucleotide polymorphisms (SNPs) of genes which either have been reported to influence the immune system, the amyloid cascade or the occurrence of PD (ApoE, GSK3B, HLA-DRA, HSPA5, SNCA, and STK39). The investigated NAb titres were neither significantly associated with the occurrence of PD, nor with demographic and clinical parameters, neurodegenerative markers or genetic variables. These results argue against a major potential of blood-borne parameters of the adaptive immune system to serve as trait or state markers in PD.
Elution Profile Analysis of SDS-induced Subcomplexes by Quantitative Mass Spectrometry
2014-02-21

Analyzing the molecular architecture of native multiprotein complexes via biochemical methods has so far been difficult and error prone. Protein complex isolation by affinity purification can define the protein repertoire of a given complex, yet, it remains difficult to gain knowledge of its substructure or modular composition. Here, we introduce SDS concentration gradient induced decomposition of protein complexes coupled to quantitative mass spectrometry and in silico elution profile distance analysis. By applying this new method to a cellular transport module, the IFT/lebercilin complex, we demonstrate its ability to determine modular composition as well as sensitively detect known and novel complex components. We show that the IFT/lebercilin complex can be separated into at least five submodules, the IFT complex A, the IFT complex B, the 14â3-3 protein complex and the CTLH complex, as well as the dynein light chain complex. Furthermore, we identify the protein TULP3 as a potential new member of the IFT complex A and showed that several proteins, classified as IFT complex B-associated, are integral parts of this complex. To further demonstrate EPASIS general applicability, we analyzed the modular substructure of two additional complexes, that of B-RAF and of 14-3-3-Îμ. The results show, that EPASIS provides a robust as well as sensitive strategy to dissect the substructure of large multiprotein complexes in a highly time- as well as cost-effective manner.
Assessing attention and cognitive function in completely locked-in state with event-related brain potentials and epidural electrocorticography
2014-02-21

Cortical electrophysiological measures indicate at least partially intact attention and cognitive function during sparse volitional motor control for communication. Although the P3 ERP and frequency-specific changes in the ECoG spectrum may serve as indicators for CLIS, a close-meshed monitoring will be required to define the exact time point of the transition.
Freshly frozen E18 rat cortical cells can generate functional neural networks after standard cryopreservation and thawing procedures
2014-02-22

Primary dissociated brain tissue from rodents is widely used in a variety of different scientific methods to investigate cellular processes in vitro. Often, for this purpose cell cultures need to be generated just on time, requiring extensive animal lab infrastructure. We show here that cryopreservation and thawing of dissociated tissue from rat cerebral cortex at embryonic day 18 is feasible without affecting its ability to form functional neuronal networks in vitro. Vitality of fresh and re-thawed cortical cells was comparable, assessed by CellTiter-Blue-assay, CytoTox-ONE assay, immunocytochemical characterization and in vitro neuronal network activity recordings on microelectrode arrays. These findings suggest that planning and execution of experiments might be considerably facilitated by using cryo-preserved neurons instead of acutely dissociated neural cultures due to fewer logistical issues with regard to animal breeding and pregnancy timed preparations.
CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice
2014-02-23

Mutations in the CRB1 gene lead to retinal dystrophies ranging from Leber congenital amaurosis (LCA) to early-onset retinitis pigmentosa (RP), due to developmental defects or loss of adhesion between photoreceptors and Müller glia cells, respectively. Whereas over 150 mutations have been found, no clear genotype-phenotype correlation has been established. Mouse Crb1 knockout retinas show a mild phenotype limited to the inferior quadrant, whereas Crb2 knockout retinas display a severe degeneration throughout the retina mimicking the phenotype observed in RP patients associated with CRB1 mutations. Crb1Crb2 double mutant retinas have severe developmental defects similar to the phenotype observed in LCA patients associated with CRB1 mutations. Therefore, CRB2 is a candidate modifying gene of human CRB1-related retinal dystrophy. In this study, we studied the cellular localization of CRB1 and CRB2 in human retina and tested the influence of the Crb2 gene allele on Crb1-retinal dystrophies in mice. We found that in contrast to mice, in the human retina CRB1 protein was expressed at the subapical region in photoreceptors and Müller glia cells, and CRB2 only in Müller glia cells. Genetic ablation of one allele of Crb2 in heterozygote Crb1(+/-) retinas induced a mild retinal phenotype, but in homozygote Crb1 knockout mice lead to an early and severe phenotype limited to the entire inferior retina. Our data provide mechanistic insight for CRB1-related LCA and RP.
Prodromal features for Parkinson's disease – baseline data from the TREND study
2014-02-24

Background and purpose A number of non‐motor features are known to precede motor manifestations of P arkinson's disease ( PD ). They are supposed to already represent the prodromal neurodegenerative state in those who later develop PD and are thus called prodromal markers. In this study, three prodromal markers, depression, rapid eye movement behaviour disorder ( RBD ) and hyposmia, were selected and were related to other prodromal features in elderly individuals without PD . Methods From the T übinger E valuation of R isk F actors for E arly Detection of N eurodegeneration ( TREND ) study, 698 healthy individuals aged 50–80 years reporting one or more of the selected prodromal markers ( SPM s), but without neurodegenerative disorders, were evaluated and classified according to the status of prodromal markers. Other prodromal PD ‐related features were assessed with a 23‐item questionnaire and compared between participants with and without the three SPMs. Results Individuals with the SPM s for PD endorsed more of the additional possible prodromal features of PD than those without; of 23 possible prodromal features, the median number identified amongst participants with no SPMs was two, compared with four with one marker, five with two and seven with three ( P &lt; 0.001). Regarding individual SPM s, participants with depression and RBD endorsed five of 23 markers, compared with three for those with hyposmia ( P = 0.001). There was no significant increase in the number of prodromal features amongst those with two SPM s compared with those with only one marker. Conclusions Individuals with the SPM s for PD report a higher prevalence of other prodromal PD symptoms. This may indicate that these markers can identify individuals at risk for PD .
Mechanisms and assessment of statin‐related muscular adverse effects
2014-02-24

Statin‐associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life‐threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin‐related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450‐mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3‐hydroxy‐3‐methylglutaryl coenzyme A ( HMG ‐ CoA ) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.