julilili42/papers huggingface dataset:
Structure and function: Lipid A modifications in commensals and pathogens
2016-03-06

Lipopolysaccharides (LPS) of Gram negative bacteria are one of the most potent stimulators of the host innate immune system and LPS recognition is essential for the host organism to clear infections of invading bacterial pathogens. Here we review on the latest research on how LPS is sensed by host cells and how distinct LPS structures differentially modulate the strength of the host immune response. Much is known about host immunological reactions towards pathogens via recognition of their LPS, as well as strategies of pathogens to modulate their LPS structure in order to evade the immune system. However, less is known about differential sensing of lipopolysaccharides of commensal bacteria in the intestine and how this contributes to manifestation or destruction of the intestinal homeostasis. LPS sensing is necessary to fight pathogens. However, sensing of LPS of gut commensal bacteria can simultaneously be disadvantageous for the genetically predisposed host, since this might lead to damage of the intestinal homeostasis and therefore to chronic intestinal inflammation. However, less immunogenic LPS could also serve as therapeutics to antagonize an overreacting innate immune system. Therefore, commensal gut bacteria-derived LPS could prevent from uncontrolled intestinal immune response in the intestine which makes LPS an attractive therapeutical approach to treat e.g. IBD.
4-Aminopyridine Induced Activity Rescues Hypoexcitable Motor Neurons from Amyotrophic Lateral Sclerosis Patient-Derived Induced Pluripotent Stem Cells
2016-03-06

Abstract Despite decades of research on amyotrophic lateral sclerosis (ALS), there is only one approved drug, which minimally extends patient survival. Here, we investigated pathophysiological mechanisms underlying ALS using motor neurons (MNs) differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying mutations in FUS or SOD1. Patient-derived MNs were less active and excitable compared to healthy controls, due to reduced Na+/K+ ratios in both ALS groups accompanied by elevated potassium channel (FUS) and attenuated sodium channel expression levels (FUS, SOD1). ALS iPSC-derived MNs showed elevated endoplasmic reticulum stress (ER) levels and increased caspase activation. Treatment with the FDA approved drug 4-Aminopyridine (4AP) restored ion-channel imbalances, increased neuronal activity levels and decreased ER stress and caspase activation. This study provides novel pathophysiological data, including a mechanistic explanation for the observed hypoexcitability in patient-derived MNs and a new therapeutic strategy to provide neuroprotection in MNs affected by ALS.
Few multiyear precipitation–reduction experiments find a shift in the productivity–precipitation relationship
2016-03-06

Abstract Well‐defined productivity–precipitation relationships of ecosystems are needed as benchmarks for the validation of land models used for future projections. The productivity–precipitation relationship may be studied in two ways: the spatial approach relates differences in productivity to those in precipitation among sites along a precipitation gradient (the spatial fit, with a steeper slope); the temporal approach relates interannual productivity changes to variation in precipitation within sites (the temporal fits, with flatter slopes). Precipitation–reduction experiments in natural ecosystems represent a complement to the fits, because they can reduce precipitation below the natural range and are thus well suited to study potential effects of climate drying. Here, we analyse the effects of dry treatments in eleven multiyear precipitation–manipulation experiments, focusing on changes in the temporal fit. We expected that structural changes in the dry treatments would occur in some experiments, thereby reducing the intercept of the temporal fit and displacing the productivity–precipitation relationship downward the spatial fit. The majority of experiments (72%) showed that dry treatments did not alter the temporal fit. This implies that current temporal fits are to be preferred over the spatial fit to benchmark land‐model projections of productivity under future climate within the precipitation ranges covered by the experiments. Moreover, in two experiments, the intercept of the temporal fit unexpectedly increased due to mechanisms that reduced either water loss or nutrient loss. The expected decrease of the intercept was observed in only one experiment, and only when distinguishing between the late and the early phases of the experiment. This implies that we currently do not know at which precipitation–reduction level or at which experimental duration structural changes will start to alter ecosystem productivity. Our study highlights the need for experiments with multiple, including more extreme, dry treatments, to identify the precipitation boundaries within which the current temporal fits remain valid.
Genetic differentiation and regional adaptation among seed origins used for grassland restoration: lessons from a multispecies transplant experiment
2016-03-07

Summary One of the key questions in ecosystem restoration is the choice of seed material for restoring plant communities. More and more scientists and practitioners are currently advocating the use of regional seed sources, based on the argument that plants are often adapted to local or regional environmental conditions, and thus, regional seed sources should provide the best restoration success. However, there is still substantial debate about this approach, partly because of a lack of solid empirical data. We conducted a multispecies transplant experiment in which we compared the performance of eight seed origins of seven plant species frequently used in grassland restoration in four common gardens across Germany. We found that, on average, plants of regional origins produced 10% more inflorescences and 7% more biomass than those of foreign origins. There were substantial differences among species in the strength of these effects, but in the majority of the study species fitness decreased with increasing geographical distance of seed origins or with increasing climatic differences between plant origins and experimental sites. In addition to these effects on plant fitness, increasing geographical or climatic distances of origin were often also correlated with increasing differences in plant phenology. Since phenology is important for biotic interactions, especially with pollinators and seed predators, using foreign seed sources may have cascading effects on local ecosystems. Synthesis and applications . Genetic differentiation is widespread in grassland species and often shows the patterns of regional adaptation. Our study thus supports the use of regional seed sources in restoration. Moreover, using non‐regional seed sources in grassland restoration may not only decrease the performance of plants, but it will likely also affect their biotic interactions.
A Microsaccadic Account of Attentional Capture and Inhibition of Return in Posner Cueing
2016-03-07

Microsaccades exhibit systematic oscillations in direction after spatial cueing, and these oscillations correlate with facilitatory and inhibitory changes in behavioral performance in the same tasks. However, independent of cueing, facilitatory and inhibitory changes in visual sensitivity also arise pre-microsaccadically. Given such pre-microsaccadic modulation, an imperative question to ask becomes: how much of task performance in spatial cueing may be attributable to these peri-movement changes in visual sensitivity? To investigate this question, we adopted a theoretical approach. We developed a minimalist model in which: (1) microsaccades are repetitively generated using a rise-to-threshold mechanism, and (2) pre-microsaccadic target onset is associated with direction-dependent modulation of visual sensitivity, as found experimentally. We asked whether such a model alone is sufficient to account for performance dynamics in spatial cueing. Our model not only explained fine-scale microsaccade frequency and direction modulations after spatial cueing, but it also generated classic facilitatory (i.e., attentional capture) and inhibitory [i.e., inhibition of return (IOR)] effects of the cue on behavioral performance. According to the model, cues reflexively reset the oculomotor system, which unmasks oscillatory processes underlying microsaccade generation; once these oscillatory processes are unmasked, "attentional capture" and "IOR" become direct outcomes of pre-microsaccadic enhancement or suppression, respectively. Interestingly, our model predicted that facilitatory and inhibitory effects on behavior should appear as a function of target onset relative to microsaccades even without prior cues. We experimentally validated this prediction for both saccadic and manual responses. We also established a potential causal mechanism for the microsaccadic oscillatory processes hypothesized by our model. We used retinal-image stabilization to experimentally control instantaneous foveal motor error during the presentation of peripheral cues, and we found that post-cue microsaccadic oscillations were severely disrupted. This suggests that microsaccades in spatial cueing tasks reflect active oculomotor correction of foveal motor error, rather than presumed oscillatory covert attentional processes. Taken together, our results demonstrate that peri-microsaccadic changes in vision can go a long way in accounting for some classic behavioral phenomena.
Uniqueness of photon spheres in electro-vacuum spacetimes
2016-03-07

In a recent paper, the authors established the uniqueness of photon spheres\\nin static vacuum asymptotically flat spacetimes by adapting Bunting and\\nMasood-ul-Alam's proof of static vacuum black hole uniqueness. Here, we\\nestablish uniqueness of suitably defined sub-extremal photon spheres in static\\nelectro-vacuum asymptotically flat spacetimes by adapting the argument of\\nMasood-ul-Alam. As a consequence of our result, we can rule out the existence\\nof electrostatic configurations involving multiple "very compact" electrically\\ncharged bodies and sub-extremal black holes.\\n
A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells
2016-03-07

Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.
Omentin-1, Adiponectin, and the Risk of Developing Type 2 Diabetes
2016-03-07

Omentin-1 is a novel adipokine (1), and its potential role in diabetes pathogenesis is still under debate (2). We aimed to evaluate the longitudinal association of omentin-1 concentrations with the risk of type 2 diabetes. This observational study was based on 2,500 randomly selected participants of the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort ( n = 27,548) (3,4). Exclusion criteria were prevalent diabetes at baseline ( n = 112), unclear diabetes status ( n = 19), and incomplete follow-up information ( n = 50). Missing biomarker information (HbA1c 14%, all others below 10%) was handled by multiple imputation. The final sample comprised 2,319 participants, including 123 incident type 2 diabetes cases. Omentin-1 plasma concentrations were quantified by a commercial sandwich ELISA (BioVendor, Brno, Czech Republic). We previously demonstrated excellent reliability of single omentin-1 measurements (5). Applied statistical methods were multivariable-adjusted linear regression (cross-sectional associations) and Cox proportional hazards regression (longitudinal association of baseline omentin-1 with ...
Evidence for a binary origin of a central compact object
2016-03-07

Central compact objects (CCOs) are thought to be young thermally emitting isolated neutron stars that were born during the preceding core-collapse supernova explosion. Here, we present evidence that at least in one case the CCO could have been formed within a binary system. We show that the highly reddened optical source IRAS 17287−3443, located 25 arcsec away from the CCO candidate XMMUJ173203.3−344518 and classified previously as a post asymptotic giant branch star, is indeed surrounded by a dust shell. This shell is heated by the central star to temperatures of ∼90 K and observed as extended infrared emission in 8–160 μm band. The dust temperature also increases in the vicinity of the CCO which implies that it likely resides within the shell. We estimate the total dust mass to be ∼0.4–1.5 M&lt;inf&gt;&amp;odot;&lt;/inf&gt; which significantly exceeds expected dust yields by normal stars and thus likely condensed from supernova ejecta. Taking into account that both the age of the supernova remnant and the duration of active mass-loss phase by the optical star are much shorter than the total lifetime of either object, the supernova and the onset of the active mass-loss phase of the companion have likely occurred approximately simultaneously. This is most easily explained if the evolution of both objects is interconnected. We conclude, therefore, that both stars were likely members of the same binary system disrupted by a supernova.
A Facile Method for the Synthesis of Binary Tungsten Iodides
2016-03-07

Abstract The preparation of tungsten iodides in large quantities is a challenge because these compounds are not accessible using an easy synthesis method. A new, remarkably efficient route is based on a halide exchange reaction between WCl 6 and SiI 4 . The reaction proceeds at moderate temperatures in a closed glass vessel. The new compounds W 3 I 12 (W 3 I 8 ⋅2 I 2 ) and W 3 I 9 (W 3 I 8 ⋅ I 2 ) containing the novel [W 3 I 8 ] cluster are formed at 120 and 150 °C, and remain stable in air. W 3 I 12 is an excellent starting material for the synthesis of other metal‐rich tungsten iodides. At increasing temperature these trinuclear clusters undergo self‐reduction until an octahedral tungsten cluster is formed in W 6 I 12 . The synthesis, structure, and an analysis of the bonding of compounds containing this new trinuclear tungsten cluster are presented.
Ancestry sampling for Indo-European phylogeny and dates
2016-03-07

Abstract—The date of the root of the Indo-European language family received much attention due to the application of Bayesian phylogenetic methods since the beginning of the last decade. The inferred root date of the family moved along with the development of new methods and better data. In this paper, I compare two dating techniques known as node-dating and total evidence dating for the Indo-European language family. I find that the total evidence dating based on a birth death tree infers age which is consistent with the Steppe hypothesis of spread of Indo-European languages.
ElSe
2016-03-08

Fast and robust pupil detection is an essential prerequisite for video-based eye-tracking in real-world settings. Several algorithms for image-based pupil detection have been proposed in the past, their applicability, however, is mostly limited to laboratory conditions. In real-world scenarios, automated pupil detection has to face various challenges, such as illumination changes, reflections (on glasses), make-up, non-centered eye recording, and physiological eye characteristics. We propose ElSe, a novel algorithm based on ellipse evaluation of a filtered edge image. We aim at a robust, inexpensive approach that can be integrated in embedded architectures, e.g., driving. The proposed algorithm was evaluated against four state-of-the-art methods on over 93,000 hand-labeled images from which 55,000 are new eye images contributed by this work. On average, the proposed method achieved a 14.53% improvement on the detection rate relative to the best state-of-the-art performer. Algorithm and data sets are available for download: ftp://[email protected] (password:eyedata).
Bayesian identification of fixations, saccades, and smooth pursuits
2016-03-08

Smooth pursuit eye movements provide meaningful insights and information on subject's behavior and health and may, in particular situations, disturb the performance of typical fixation/saccade classification algorithms. Thus, an automatic and efficient algorithm to identify these eye movements is paramount for eye-tracking research involving dynamic stimuli. In this paper, we propose the Bayesian Decision Theory Identification (I-BDT) algorithm, a novel algorithm for ternary classification of eye movements that is able to reliably separate fixations, saccades, and smooth pursuits in an online fashion, even for low-resolution eye trackers. The proposed algorithm is evaluated on four datasets with distinct mixtures of eye movements, including fixations, saccades, as well as straight and circular smooth pursuits; data was collected with a sample rate of 30 Hz from six subjects, totaling 24 evaluation datasets. The algorithm exhibits high and consistent performance across all datasets and movements relative to a manual annotation by a domain expert (recall: μ = 91.42%, σ = 9.52%; precision: μ = 95.60%, σ = 5.29%; specificity μ = 95.41%, σ = 7.02%) and displays a significant improvement when compared to I-VDT, an state-of-the-art algorithm (recall: μ = 87.67%, σ = 14.73%; precision: μ = 89.57%, σ = 8.05%; specificity μ = 92.10%, σ = 11.21%). Algorithm implementation and annotated datasets are openly available at www.ti.uni-tuebingen.de/perception
The cyclochlorotine mycotoxin is produced by the nonribosomal peptide synthetase CctN in Talaromyces islandicus (‘ Penicillium islandicum ’)
2016-03-08

Summary Talaromyces islandicus (‘ Penicillium islandicum ’) is a widespread foodborne mold that produces numerous secondary metabolites, among them potent mycotoxins belonging to different chemical classes. A notable metabolite is the hepatotoxic and carcinogenic pentapeptide cyclochlorotine that contains the unusual amino acids β‐phenylalanine, 2‐aminobutyrate and 3,4‐dichloroproline. Although the chemical structure has been known for over five decades, nothing is known about the biosynthetic pathway of cyclochlorotine. Bioinformatic analysis of the recently sequenced genome of T. islandicus identified a wealth of gene clusters potentially coding for the synthesis of secondary metabolites. Here, we show by RNA interference‐mediated gene silencing that a nonribosomal peptide synthetase, CctN, is responsible for the synthesis of cyclochlorotine. Moreover, we identified novel cyclochlorotine chemical variants, whose production also depended on cctN expression. Surprisingly, the halogenase required for cyclochlorotine biosynthesis is not encoded in the cct cluster. Nonetheless, our findings enabled us to propose a detailed model for cyclochlorotine biosynthesis. In addition, comparative genomics revealed that cct ‐like clusters are present in all of the sequenced Talaromyces strains indicating a high prevalence of cyclochlorotine production ability.
Dismissing Attachment Characteristics Dynamically Modulate Brain Networks Subserving Social Aversion
2016-03-08

Attachment patterns influence actions, thoughts and feeling through a person's "inner working model". Speech charged with attachment-dependent content was proposed to modulate the activation of cognitive-emotional schemata in listeners. We performed a 7 Tesla rest-task-rest functional magnetic resonance imaging (fMRI)-experiment, presenting auditory narratives prototypical of dismissing attachment representations to investigate their effect on 23 healthy males. We then examined effects of participants' attachment style and childhood trauma on brain state changes using seed-based functional connectivity (FC) analyses, and finally tested whether subjective differences in responsivity to narratives could be predicted by baseline network states. In comparison to a baseline state, we observed increased FC in a previously described "social aversion network" including dorsal anterior cingulated cortex (dACC) and left anterior middle temporal gyrus (aMTG) specifically after exposure to insecure-dismissing attachment narratives. Increased dACC-seeded FC within the social aversion network was positively related to the participants' avoidant attachment style and presence of a history of childhood trauma. Anxious attachment style on the other hand was positively correlated with FC between the dACC and a region outside of the "social aversion network", namely the dorsolateral prefrontal cortex, which suggests decreased network segregation as a function of anxious attachment. Finally, the extent of subjective experience of friendliness towards the dismissing narrative was predicted by low baseline FC-values between hippocampus and inferior parietal lobule (IPL). Taken together, our study demonstrates an activation of networks related to social aversion in terms of increased connectivity after listening to insecure-dismissing attachment narratives. A causal interrelation of brain state changes and subsequent changes in social reactivity was further supported by our observation of direct prediction of neuronal responses by individual attachment and trauma characteristics and reversely prediction of subjective experience by intrinsic functional connections. We consider these findings of activation of within-network and between-network connectivity modulated by inter-individual differences as substantial for the understanding of interpersonal processes, particularly in clinical settings.